Rheumatoid Arthritis

Patients with inflammatory joint diseases who participated in a 10-session mindfulness-based group intervention experienced significant lessening of psychological distress and improvement in self-efficacy, emotional processing, and overall well-being at 6 and 12 months, judging from the results from a randomized controlled trial.

"These lasting improvements indicate that the participants may have incorporated some mindfulness strategies into their daily lives and that these strategies have strengthened their ability to respond to their stressful experiences in a more flexible way," according to Heidi A. Zangi, Ph.D., of the department of rheumatology at Diakonhjemmet Hospital, Oslo, Norway, and her associates (Ann. Rheum. Dis. 2011 Dec. 20 [doi: 10.1136/annrheumdis-2011-200351]).

For the study, which was conducted at three rheumatology departments in Norway between March 2007 and June 2009, Dr. Zangi and her associates randomized 71 adults aged 20-70 years who were diagnosed with an inflammatory rheumatic joint disease at least 1 year earlier to a mindfulness-based group intervention known as the Vitality Training Program (VTP) or to a control group. Patients assigned to the control group received routine care plus a compact disc with mindfulness-based home exercises for individual voluntary use.

The investigators described VTP as an intervention aimed at "strengthening the personal resources of individuals and enhancing their capacity to engage responsibly and satisfactorily in the process of everyday living." Such an approach, they wrote, advocates "the importance of nonjudgmental attention to unwanted thoughts, feelings, and bodily experiences without attempting to avoid or change them."

The VTP consisted of 10 group sessions over a period of 15 weeks, plus a "booster session" that took place about 6 months after the end of the course. Patients in the control group were informed that they would have the opportunity to participate in the VTP after completion of data collection. Patients in both groups received routine medical care throughout the study.

Of 814 patients who were invited to enroll in the study, 71 participated. Of these, 36 were randomized to the VTP arm and 35 to the control arm. The primary outcome measure was psychological distress as measured by the 20-item version of the General Health Questionnaire. In this tool, a sum score can range from 0 (no distress) to 60 (high distress). Co-primary outcomes were self-efficacy, as measured by the pain and symptoms subscales of the Arthritis Self-Efficacy Scale, and emotion-focused coping, as measured by the Emotional Approach Coping Scale.

Secondary outcomes were assessed by numerical rating scales ranging from 0 to 10 (where 10 is very bad) and included pain, fatigue, and patient-reported global assessment of disease activity. All patients were assessed at baseline, at post-treatment, and at 12 months.

The mean age of patients was 54 years, and 79% were women. After adjusting for gender, age, disease duration, and education, the researchers observed significant mean treatment effects in favor of the VTP at post-treatment and at 12 months for the following outcomes: psychological distress (–4.7 and –3.7, respectively), self-efficacy pain (8.2 and 9.1), self-efficacy symptoms (8.8 and 13.1), emotional processing (0.4 and 0.3), fatigue (–0.8, –1.1), self-care ability (1.2 and 1.0), and overall well-being (0.8 and 0.6). No significant group differences were found in emotional expression, pain, or disease activity.

Dr. Zangi and her associates acknowledged certain limitations of the study, including the fact that all outcome measures were patient reported, and that so few of the patients invited to participate chose to do so, "which probably reflects a selection bias in the direction of highly motivated individuals," they wrote. "Consequently, the results cannot be generalized to the whole population of persons with inflammatory arthritis. However, from our clinical experience we know that there are waiting lists for the existing VTP courses, and that the low uptake may partly be explained by unwillingness to participate in a randomized controlled trial."

The study was supported by Diakonhjemmet Hospital. The investigators reported that they did not have any competing financial interests.

Patients with inflammatory joint diseases who participated in a 10-session mindfulness-based group intervention experienced significant lessening of psychological distress and improvement in self-efficacy, emotional processing, and overall well-being at 6 and 12 months, judging from the results from a randomized controlled trial.

"These lasting improvements indicate that the participants may have incorporated some mindfulness strategies into their daily lives and that these strategies have strengthened their ability to respond to their stressful experiences in a more flexible way," according to Heidi A. Zangi, Ph.D., of the department of rheumatology at Diakonhjemmet Hospital, Oslo, Norway, and her associates (Ann. Rheum. Dis. 2011 Dec. 20 [doi: 10.1136/annrheumdis-2011-200351]).

For the study, which was conducted at three rheumatology departments in Norway between March 2007 and June 2009, Dr. Zangi and her associates randomized 71 adults aged 20-70 years who were diagnosed with an inflammatory rheumatic joint disease at least 1 year earlier to a mindfulness-based group intervention known as the Vitality Training Program (VTP) or to a control group. Patients assigned to the control group received routine care plus a compact disc with mindfulness-based home exercises for individual voluntary use.

The investigators described VTP as an intervention aimed at "strengthening the personal resources of individuals and enhancing their capacity to engage responsibly and satisfactorily in the process of everyday living." Such an approach, they wrote, advocates "the importance of nonjudgmental attention to unwanted thoughts, feelings, and bodily experiences without attempting to avoid or change them."

The VTP consisted of 10 group sessions over a period of 15 weeks, plus a "booster session" that took place about 6 months after the end of the course. Patients in the control group were informed that they would have the opportunity to participate in the VTP after completion of data collection. Patients in both groups received routine medical care throughout the study.

Of 814 patients who were invited to enroll in the study, 71 participated. Of these, 36 were randomized to the VTP arm and 35 to the control arm. The primary outcome measure was psychological distress as measured by the 20-item version of the General Health Questionnaire. In this tool, a sum score can range from 0 (no distress) to 60 (high distress). Co-primary outcomes were self-efficacy, as measured by the pain and symptoms subscales of the Arthritis Self-Efficacy Scale, and emotion-focused coping, as measured by the Emotional Approach Coping Scale.

Secondary outcomes were assessed by numerical rating scales ranging from 0 to 10 (where 10 is very bad) and included pain, fatigue, and patient-reported global assessment of disease activity. All patients were assessed at baseline, at post-treatment, and at 12 months.

The mean age of patients was 54 years, and 79% were women. After adjusting for gender, age, disease duration, and education, the researchers observed significant mean treatment effects in favor of the VTP at post-treatment and at 12 months for the following outcomes: psychological distress (–4.7 and –3.7, respectively), self-efficacy pain (8.2 and 9.1), self-efficacy symptoms (8.8 and 13.1), emotional processing (0.4 and 0.3), fatigue (–0.8, –1.1), self-care ability (1.2 and 1.0), and overall well-being (0.8 and 0.6). No significant group differences were found in emotional expression, pain, or disease activity.

Dr. Zangi and her associates acknowledged certain limitations of the study, including the fact that all outcome measures were patient reported, and that so few of the patients invited to participate chose to do so, "which probably reflects a selection bias in the direction of highly motivated individuals," they wrote. "Consequently, the results cannot be generalized to the whole population of persons with inflammatory arthritis. However, from our clinical experience we know that there are waiting lists for the existing VTP courses, and that the low uptake may partly be explained by unwillingness to participate in a randomized controlled trial."

The study was supported by Diakonhjemmet Hospital. The investigators reported that they did not have any competing financial interests.

Patients with inflammatory joint diseases who participated in a 10-session mindfulness-based group intervention experienced significant lessening of psychological distress and improvement in self-efficacy, emotional processing, and overall well-being at 6 and 12 months, judging from the results from a randomized controlled trial.

"These lasting improvements indicate that the participants may have incorporated some mindfulness strategies into their daily lives and that these strategies have strengthened their ability to respond to their stressful experiences in a more flexible way," according to Heidi A. Zangi, Ph.D., of the department of rheumatology at Diakonhjemmet Hospital, Oslo, Norway, and her associates (Ann. Rheum. Dis. 2011 Dec. 20 [doi: 10.1136/annrheumdis-2011-200351]).

For the study, which was conducted at three rheumatology departments in Norway between March 2007 and June 2009, Dr. Zangi and her associates randomized 71 adults aged 20-70 years who were diagnosed with an inflammatory rheumatic joint disease at least 1 year earlier to a mindfulness-based group intervention known as the Vitality Training Program (VTP) or to a control group. Patients assigned to the control group received routine care plus a compact disc with mindfulness-based home exercises for individual voluntary use.

The investigators described VTP as an intervention aimed at "strengthening the personal resources of individuals and enhancing their capacity to engage responsibly and satisfactorily in the process of everyday living." Such an approach, they wrote, advocates "the importance of nonjudgmental attention to unwanted thoughts, feelings, and bodily experiences without attempting to avoid or change them."

The VTP consisted of 10 group sessions over a period of 15 weeks, plus a "booster session" that took place about 6 months after the end of the course. Patients in the control group were informed that they would have the opportunity to participate in the VTP after completion of data collection. Patients in both groups received routine medical care throughout the study.

Of 814 patients who were invited to enroll in the study, 71 participated. Of these, 36 were randomized to the VTP arm and 35 to the control arm. The primary outcome measure was psychological distress as measured by the 20-item version of the General Health Questionnaire. In this tool, a sum score can range from 0 (no distress) to 60 (high distress). Co-primary outcomes were self-efficacy, as measured by the pain and symptoms subscales of the Arthritis Self-Efficacy Scale, and emotion-focused coping, as measured by the Emotional Approach Coping Scale.

Secondary outcomes were assessed by numerical rating scales ranging from 0 to 10 (where 10 is very bad) and included pain, fatigue, and patient-reported global assessment of disease activity. All patients were assessed at baseline, at post-treatment, and at 12 months.

The mean age of patients was 54 years, and 79% were women. After adjusting for gender, age, disease duration, and education, the researchers observed significant mean treatment effects in favor of the VTP at post-treatment and at 12 months for the following outcomes: psychological distress (–4.7 and –3.7, respectively), self-efficacy pain (8.2 and 9.1), self-efficacy symptoms (8.8 and 13.1), emotional processing (0.4 and 0.3), fatigue (–0.8, –1.1), self-care ability (1.2 and 1.0), and overall well-being (0.8 and 0.6). No significant group differences were found in emotional expression, pain, or disease activity.

Dr. Zangi and her associates acknowledged certain limitations of the study, including the fact that all outcome measures were patient reported, and that so few of the patients invited to participate chose to do so, "which probably reflects a selection bias in the direction of highly motivated individuals," they wrote. "Consequently, the results cannot be generalized to the whole population of persons with inflammatory arthritis. However, from our clinical experience we know that there are waiting lists for the existing VTP courses, and that the low uptake may partly be explained by unwillingness to participate in a randomized controlled trial."

The study was supported by Diakonhjemmet Hospital. The investigators reported that they did not have any competing financial interests.

Men with rheumatoid arthritis have a two-thirds greater risk of developing erectile dysfunction than men without the disease, based on the results of the first study to show such an association.

The odds ratio for prior rheumatoid arthritis (RA) among men with erectile dysfunction (ED) was 1.67 that of controls, based on conditional logistic regression analysis, after adjusting for the possible confounding effects of monthly income, geographical location, urbanization level, hypertension, diabetes, coronary heart disease, hyperlipidemia, obesity, and alcohol abuse/alcohol dependence syndrome. The study was published in a letter in Annals of the Rheumatic Diseases on Jan. 4 (Ann. Rheum. Dis. 2011 Jan. 4 [doi:10.1136/annrheumdis-2011-200890]).

"This study succeeded in making a novel association between ED and prior RA. It is important for physicians treating RA patients to be sensitive to any complaints concerning sexual function and consider referring them for an erectile function assessment and possible treatment," wrote Dr. Joseph J Keller and Herng-Ching Lin, Ph.D., of the Taipei (Taiwan) Medical University.

The study included 6,310 patients (aged 18-80 years) who had received a first-time diagnosis of ED between 2001 and 2009 as cases and 37,860 control patients (six controls per case) were matched with cases in terms of age (in intervals of 10 years) and index year.

"It is important for physicians treating RA patients to be sensitive to any complaints concerning sexual function."

The researchers used administrative claims data from the Taiwan Longitudinal Health Insurance Database 2000 for this study. The database includes all the claims data and registration files of 1 million individuals under the Taiwan National Health Insurance program.

The researchers included only ED patients who had been diagnosed at least twice during the period between 2001 and 2009 – with at least one of the diagnoses being made by a urologist – in order to increase the diagnostic validity of ED.

The researchers also selected patients with RA who had received two or more RA diagnoses prior to the index date – with at least one being made by a rheumatologist. In addition, RA cases were included only if they had been prescribed at least one type of disease-modifying antirheumatic drug.

It has been suggested that patients with RA may be more likely to develop other conditions – such as ED – that are associated with increased cardiovascular risks and chronic inflammation. However, no study has explored the possible association between ED and RA to date.

The researchers noted that "it is possible that the association seen in this study between RA and ED proceeds through RA-induced endothelial dysfunction. Although a plethora of mechanisms have been proposed to underpin ED’s association with other diseases. ... [F]urther studies will be necessary to explore the mechanistic underpinnings of the association detected in this study."

Both authors reported that they have no competing interests.

Men with rheumatoid arthritis have a two-thirds greater risk of developing erectile dysfunction than men without the disease, based on the results of the first study to show such an association.

The odds ratio for prior rheumatoid arthritis (RA) among men with erectile dysfunction (ED) was 1.67 that of controls, based on conditional logistic regression analysis, after adjusting for the possible confounding effects of monthly income, geographical location, urbanization level, hypertension, diabetes, coronary heart disease, hyperlipidemia, obesity, and alcohol abuse/alcohol dependence syndrome. The study was published in a letter in Annals of the Rheumatic Diseases on Jan. 4 (Ann. Rheum. Dis. 2011 Jan. 4 [doi:10.1136/annrheumdis-2011-200890]).

"This study succeeded in making a novel association between ED and prior RA. It is important for physicians treating RA patients to be sensitive to any complaints concerning sexual function and consider referring them for an erectile function assessment and possible treatment," wrote Dr. Joseph J Keller and Herng-Ching Lin, Ph.D., of the Taipei (Taiwan) Medical University.

The study included 6,310 patients (aged 18-80 years) who had received a first-time diagnosis of ED between 2001 and 2009 as cases and 37,860 control patients (six controls per case) were matched with cases in terms of age (in intervals of 10 years) and index year.

"It is important for physicians treating RA patients to be sensitive to any complaints concerning sexual function."

The researchers used administrative claims data from the Taiwan Longitudinal Health Insurance Database 2000 for this study. The database includes all the claims data and registration files of 1 million individuals under the Taiwan National Health Insurance program.

The researchers included only ED patients who had been diagnosed at least twice during the period between 2001 and 2009 – with at least one of the diagnoses being made by a urologist – in order to increase the diagnostic validity of ED.

The researchers also selected patients with RA who had received two or more RA diagnoses prior to the index date – with at least one being made by a rheumatologist. In addition, RA cases were included only if they had been prescribed at least one type of disease-modifying antirheumatic drug.

It has been suggested that patients with RA may be more likely to develop other conditions – such as ED – that are associated with increased cardiovascular risks and chronic inflammation. However, no study has explored the possible association between ED and RA to date.

The researchers noted that "it is possible that the association seen in this study between RA and ED proceeds through RA-induced endothelial dysfunction. Although a plethora of mechanisms have been proposed to underpin ED’s association with other diseases. ... [F]urther studies will be necessary to explore the mechanistic underpinnings of the association detected in this study."

Both authors reported that they have no competing interests.

Men with rheumatoid arthritis have a two-thirds greater risk of developing erectile dysfunction than men without the disease, based on the results of the first study to show such an association.

The odds ratio for prior rheumatoid arthritis (RA) among men with erectile dysfunction (ED) was 1.67 that of controls, based on conditional logistic regression analysis, after adjusting for the possible confounding effects of monthly income, geographical location, urbanization level, hypertension, diabetes, coronary heart disease, hyperlipidemia, obesity, and alcohol abuse/alcohol dependence syndrome. The study was published in a letter in Annals of the Rheumatic Diseases on Jan. 4 (Ann. Rheum. Dis. 2011 Jan. 4 [doi:10.1136/annrheumdis-2011-200890]).

"This study succeeded in making a novel association between ED and prior RA. It is important for physicians treating RA patients to be sensitive to any complaints concerning sexual function and consider referring them for an erectile function assessment and possible treatment," wrote Dr. Joseph J Keller and Herng-Ching Lin, Ph.D., of the Taipei (Taiwan) Medical University.

The study included 6,310 patients (aged 18-80 years) who had received a first-time diagnosis of ED between 2001 and 2009 as cases and 37,860 control patients (six controls per case) were matched with cases in terms of age (in intervals of 10 years) and index year.

"It is important for physicians treating RA patients to be sensitive to any complaints concerning sexual function."

The researchers used administrative claims data from the Taiwan Longitudinal Health Insurance Database 2000 for this study. The database includes all the claims data and registration files of 1 million individuals under the Taiwan National Health Insurance program.

The researchers included only ED patients who had been diagnosed at least twice during the period between 2001 and 2009 – with at least one of the diagnoses being made by a urologist – in order to increase the diagnostic validity of ED.

The researchers also selected patients with RA who had received two or more RA diagnoses prior to the index date – with at least one being made by a rheumatologist. In addition, RA cases were included only if they had been prescribed at least one type of disease-modifying antirheumatic drug.

It has been suggested that patients with RA may be more likely to develop other conditions – such as ED – that are associated with increased cardiovascular risks and chronic inflammation. However, no study has explored the possible association between ED and RA to date.

The researchers noted that "it is possible that the association seen in this study between RA and ED proceeds through RA-induced endothelial dysfunction. Although a plethora of mechanisms have been proposed to underpin ED’s association with other diseases. ... [F]urther studies will be necessary to explore the mechanistic underpinnings of the association detected in this study."

Both authors reported that they have no competing interests.

NEW YORK – Among new medications under development for rheumatoid arthritis, oral Janus kinase inhibitors appear to be close to coming to market and have strong supportive clinical data, according to Dr. Martin Jan Bergman at a course sponsored by New York University.

Unlike most drugs for RA that affect extracellular cytokines, oral JAK inhibitors are small molecules that act to disrupt one of the intracellular signal pathways used by some cytokines to regulate immune and regulatory responses. Of this family of drugs, Pfizer’s tofacitinib primarily targets JAK3 (the JAK protein kinase that is most associated with inflammation), although it also overlaps to JAK1 and JAK2.

On Dec. 20, Pfizer announced that the Food and Drug Administration has accepted a New Drug Application for tofacitinib, formerly known as tasocitinib. About 1 month earlier, the European Medicines Agency had taken similar action, according to Pfizer.

According to Pfizer, nearly 5,000 patients with RA have undergone treatment in clinical trials of tofacitinib held at more than 350 sites in 35 countries worldwide. The data come primarily from the ORAL (Oral Rheumatoid Arthritis Phase III) trials, comprising five studies for which the data necessary for registration are complete, and one ongoing phase III trial. Two long-term, open-label extension studies are also ongoing.

During his presentation, Dr. Bergman reviewed data presented in 2001 at the annual European Congress of Rheumatology by Dr. Joel M. Kremer, head of the division of rheumatology at Albany (N.Y.) Medical College. Those data concerned the effects of tofacitinib in patients whose active RA had not responded to therapy with DMARDs (disease-modifying antirheumatic drugs). Patients received tofacitinib in doses of either 5 mg or 10 mg, in combination with background DMARDs. In this double-blind, placebo-controlled, randomized study of 792 patients, any patient in the placebo group who had not met the target efficacy response by 3 months was switched to tofacitinib 5 mg or 10 mg. All remaining placebo-treated patients were switched to tofacitinib by 6 months. At 6 months, 52.7% in those treated with tofacitinib 5 mg achieved ACR 20 (defined as 20% improvement on an American College of Rheumatology evaluation scale), as did 58.3% in those treated at the 10-mg dose, a response significantly greater than the placebo group. "Now we are starting to see levels that we see with [tumor necrosis factor] inhibitors," said Dr. Bergman of Drexel University in Philadelphia.

Dr. Kremer also found significant improvement on the DAS28-4 (ESR) – that is, the Disease Activity Score including a 28-joint count and the erythrocyte sedimentation rate – less than 2.6 for both doses of tofacitinib, as well as on the HAQ-DI (Health Assessment Questionnaire–Disability Index). "The minimally clinically important (MCI) difference for the HAQ-DI is 0.21 or 0.23; patients on tofacitinib had double the MCI improvement," noted Dr. Bergman, referring to the change of –0.46 for the 5-mg dose and –0.56 for the 10-mg dose (P less than .001, compared with placebo, for both differences). "What we see is very reassuring."

Dr. Bergman then highlighted some of data included in nine abstracts presented on tofacitinib at the 2011 annual meeting of the American College of Rheumatology. Dr. Roy M. Fleischmann of the University of Texas Southwestern Medical Center, Dallas, addressed the question of whether tofacitinib’s efficacy and safety hold up against the standard of care, such as a tumor necrosis factor (TNF) inhibitor (Arthritis Rheum. 2011;63[suppl.]:S153; abstract 408). In this 12-month trial, 717 patients were randomized to tofacitinib (5 mg or 10 mg twice daily), adalimumab (40-mg subcutaneous injections every 2 weeks), or placebo. "This was not a head-to-head trial, but rather comparability vs. placebo," commented Dr. Bergman. The results showed that tofacitinib 5 mg and 10 mg, as well as adalimumab, were statistically superior to placebo for all primary efficacy end points, and efficacy results for tofacitinib and adalimumab were numerically similar. "The ACR 20 responses (tofacitinib 5 mg, 51.5%; tofacitinib 10 mg, 52.6%; adalimumab, 47.2%) are very robust and comparable to the responses we see [with anti-TNFs] all the time," he added.

Tofacitinib also holds promise as a rescue therapy for RA patients with inadequate response to TNF inhibitors, as suggested by the results of a study by Dr. Gerd-Rüdiger Burmester of Charité Medical University Berlin (Arthritis Rheum. 2011;63[suppl.]:S279; abstract 718). In this 6-month study of 399 patients who were randomized to 5 mg or 10 mg of tofacitinib or placebo (or who were first treated with placebo and then given tofacitinib), rapid, significant and clinically meaningful improvements were noted in the signs and symptoms of RA (according to ACR 20/50/70 scores), physical functioning (per HAQ-DI scores) and disease activity (per DAS28-4 [ESR] scores less than 2.6). After looking at the ACR responses of the group that was initially given placebo and then 5-mg tofacitinib, Dr. Bergman commented that the 6-month ACR 20/50/70 responses (45.5, 28.79, and 10.6, respectively) were "identical to what we see with all of the rescue therapies currently available."

Interim results of a 24-month study regarding the effect of tofacitinib on radiographic progression were reported by Dr. Désirée van der Heijde of the department of rheumatology at Leiden (the Netherlands) University Medical Center (Arthritis Rheum. 2011;63[suppl.]:S1017-8; abstract 2592). The study included 797 patients with active RA who had a history of inadequate response to methotrexate and were on a stable dose of methotrexate. After 6 months of treatment, the mean change in the mTSS (modified Total Sharp Score) for tofacitinib 10 mg twice daily was 0.06, which was significantly lower (P less than .05) than placebo (mTSS, 0.47), indicating reduced progression of structural damage. The difference was not statistically significant for the 5-mg tofacitinib dose, in which the mTSS was 0.12.

In reviewing Dr. van der Heijde’s findings, Dr. Bergman questioned whether even a mean change of mTSS of 0.47 – on a scale of 0-400 – was clinically meaningful. At 12 months, the proportion of patients with no radiographic progression or no new erosions was greater in both tofacitinib groups, compared with placebo. "I don’t think we should make too much of these results, but I think the findings are reassuring that this oral medication has effects similar to the anti-TNFs," commented Dr. Bergman.

According to Dr. Bergman, more safety data are available for tofacitinib than for any other RA drug currently on the market, given its stage of development, especially as measured by patient-years. Two abstracts at the ACR annual meeting reported on long-term safety data, one summarizing pooled data from five randomized, double-blind, phase III studies, and two long-term, open-label extension studies (Arthritis Rheum. 2011;63[suppl.]:S153; abstract 409) and the other just from the same two long-term, open-label extension studies (Arthritis Rheum. 2011;63[suppl.]:S152-3; abstract 407). The former was an analysis by Dr. Stanley B. Cohen, a rheumatologist at the University of Texas, Dallas. It included 3,030 RA patients from the phase III trials and 3,227 from the long-term extensions, resulting in approximately 2,000 and 3,000 patient-years of exposure to tofacitinib. In the phase III studies, there were 12 deaths, with a death rate of 0.40% with tofacitinib (5 deaths caused by infections, and 2 with cardiovascular causes), and 8 deaths in the long-term extensions (3 from infections, and 1 with a cardiovascular cause), with a death rate of 0.62%; the rate for placebo was 0.15%. This rate was comparable with that reported for adalimumab (0.49%).

The rates of serious infections were 2% in the tofacitinib phase III studies, and 2.9% in the tofacitinib long-term extensions, compared with 1.5% for adalimumab. There was some indication in the long-term extension data that the higher dose was associated with more serious infections than was the lower dose. Whether tofacitinib was given as monotherapy or with background DMARDs did not change the infection rate. Opportunistic infections, including tuberculosis, were uncommon.

In the second analysis, based on data from the long-term extension studies and reported by Dr. Jürgen Wollenhaupt of the University of Hamburg (Germany), there were some adverse events to "keep an eye out for," commented Dr. Bergman. This report represented data on 3,227 patients who were treated for a total duration of 3,118 patient-years. Serious adverse events were reported in 10.5% of patients. Confirmed increases in creatinine (defined as greater than 33% from baseline) were found in 12.2% of patients. Decreased hemoglobin levels (greater than or equal to 2 g/dL or less than 8) were found in 2.5% of patients, and raised aminotransferase levels (defined as greater than three times the upper limit of normal) were found in 1.7% (alanine) and 1.1% (aspartate) of patients. A 15% persistent rise across all doses was seen in total cholesterol. Diarrhea may also be a problem for some patients.

Dr. Bergman serves as a consultant to Pfizer.

NEW YORK – Among new medications under development for rheumatoid arthritis, oral Janus kinase inhibitors appear to be close to coming to market and have strong supportive clinical data, according to Dr. Martin Jan Bergman at a course sponsored by New York University.

Unlike most drugs for RA that affect extracellular cytokines, oral JAK inhibitors are small molecules that act to disrupt one of the intracellular signal pathways used by some cytokines to regulate immune and regulatory responses. Of this family of drugs, Pfizer’s tofacitinib primarily targets JAK3 (the JAK protein kinase that is most associated with inflammation), although it also overlaps to JAK1 and JAK2.

On Dec. 20, Pfizer announced that the Food and Drug Administration has accepted a New Drug Application for tofacitinib, formerly known as tasocitinib. About 1 month earlier, the European Medicines Agency had taken similar action, according to Pfizer.

According to Pfizer, nearly 5,000 patients with RA have undergone treatment in clinical trials of tofacitinib held at more than 350 sites in 35 countries worldwide. The data come primarily from the ORAL (Oral Rheumatoid Arthritis Phase III) trials, comprising five studies for which the data necessary for registration are complete, and one ongoing phase III trial. Two long-term, open-label extension studies are also ongoing.

During his presentation, Dr. Bergman reviewed data presented in 2001 at the annual European Congress of Rheumatology by Dr. Joel M. Kremer, head of the division of rheumatology at Albany (N.Y.) Medical College. Those data concerned the effects of tofacitinib in patients whose active RA had not responded to therapy with DMARDs (disease-modifying antirheumatic drugs). Patients received tofacitinib in doses of either 5 mg or 10 mg, in combination with background DMARDs. In this double-blind, placebo-controlled, randomized study of 792 patients, any patient in the placebo group who had not met the target efficacy response by 3 months was switched to tofacitinib 5 mg or 10 mg. All remaining placebo-treated patients were switched to tofacitinib by 6 months. At 6 months, 52.7% in those treated with tofacitinib 5 mg achieved ACR 20 (defined as 20% improvement on an American College of Rheumatology evaluation scale), as did 58.3% in those treated at the 10-mg dose, a response significantly greater than the placebo group. "Now we are starting to see levels that we see with [tumor necrosis factor] inhibitors," said Dr. Bergman of Drexel University in Philadelphia.

Dr. Kremer also found significant improvement on the DAS28-4 (ESR) – that is, the Disease Activity Score including a 28-joint count and the erythrocyte sedimentation rate – less than 2.6 for both doses of tofacitinib, as well as on the HAQ-DI (Health Assessment Questionnaire–Disability Index). "The minimally clinically important (MCI) difference for the HAQ-DI is 0.21 or 0.23; patients on tofacitinib had double the MCI improvement," noted Dr. Bergman, referring to the change of –0.46 for the 5-mg dose and –0.56 for the 10-mg dose (P less than .001, compared with placebo, for both differences). "What we see is very reassuring."

Dr. Bergman then highlighted some of data included in nine abstracts presented on tofacitinib at the 2011 annual meeting of the American College of Rheumatology. Dr. Roy M. Fleischmann of the University of Texas Southwestern Medical Center, Dallas, addressed the question of whether tofacitinib’s efficacy and safety hold up against the standard of care, such as a tumor necrosis factor (TNF) inhibitor (Arthritis Rheum. 2011;63[suppl.]:S153; abstract 408). In this 12-month trial, 717 patients were randomized to tofacitinib (5 mg or 10 mg twice daily), adalimumab (40-mg subcutaneous injections every 2 weeks), or placebo. "This was not a head-to-head trial, but rather comparability vs. placebo," commented Dr. Bergman. The results showed that tofacitinib 5 mg and 10 mg, as well as adalimumab, were statistically superior to placebo for all primary efficacy end points, and efficacy results for tofacitinib and adalimumab were numerically similar. "The ACR 20 responses (tofacitinib 5 mg, 51.5%; tofacitinib 10 mg, 52.6%; adalimumab, 47.2%) are very robust and comparable to the responses we see [with anti-TNFs] all the time," he added.

Tofacitinib also holds promise as a rescue therapy for RA patients with inadequate response to TNF inhibitors, as suggested by the results of a study by Dr. Gerd-Rüdiger Burmester of Charité Medical University Berlin (Arthritis Rheum. 2011;63[suppl.]:S279; abstract 718). In this 6-month study of 399 patients who were randomized to 5 mg or 10 mg of tofacitinib or placebo (or who were first treated with placebo and then given tofacitinib), rapid, significant and clinically meaningful improvements were noted in the signs and symptoms of RA (according to ACR 20/50/70 scores), physical functioning (per HAQ-DI scores) and disease activity (per DAS28-4 [ESR] scores less than 2.6). After looking at the ACR responses of the group that was initially given placebo and then 5-mg tofacitinib, Dr. Bergman commented that the 6-month ACR 20/50/70 responses (45.5, 28.79, and 10.6, respectively) were "identical to what we see with all of the rescue therapies currently available."

Interim results of a 24-month study regarding the effect of tofacitinib on radiographic progression were reported by Dr. Désirée van der Heijde of the department of rheumatology at Leiden (the Netherlands) University Medical Center (Arthritis Rheum. 2011;63[suppl.]:S1017-8; abstract 2592). The study included 797 patients with active RA who had a history of inadequate response to methotrexate and were on a stable dose of methotrexate. After 6 months of treatment, the mean change in the mTSS (modified Total Sharp Score) for tofacitinib 10 mg twice daily was 0.06, which was significantly lower (P less than .05) than placebo (mTSS, 0.47), indicating reduced progression of structural damage. The difference was not statistically significant for the 5-mg tofacitinib dose, in which the mTSS was 0.12.

In reviewing Dr. van der Heijde’s findings, Dr. Bergman questioned whether even a mean change of mTSS of 0.47 – on a scale of 0-400 – was clinically meaningful. At 12 months, the proportion of patients with no radiographic progression or no new erosions was greater in both tofacitinib groups, compared with placebo. "I don’t think we should make too much of these results, but I think the findings are reassuring that this oral medication has effects similar to the anti-TNFs," commented Dr. Bergman.

According to Dr. Bergman, more safety data are available for tofacitinib than for any other RA drug currently on the market, given its stage of development, especially as measured by patient-years. Two abstracts at the ACR annual meeting reported on long-term safety data, one summarizing pooled data from five randomized, double-blind, phase III studies, and two long-term, open-label extension studies (Arthritis Rheum. 2011;63[suppl.]:S153; abstract 409) and the other just from the same two long-term, open-label extension studies (Arthritis Rheum. 2011;63[suppl.]:S152-3; abstract 407). The former was an analysis by Dr. Stanley B. Cohen, a rheumatologist at the University of Texas, Dallas. It included 3,030 RA patients from the phase III trials and 3,227 from the long-term extensions, resulting in approximately 2,000 and 3,000 patient-years of exposure to tofacitinib. In the phase III studies, there were 12 deaths, with a death rate of 0.40% with tofacitinib (5 deaths caused by infections, and 2 with cardiovascular causes), and 8 deaths in the long-term extensions (3 from infections, and 1 with a cardiovascular cause), with a death rate of 0.62%; the rate for placebo was 0.15%. This rate was comparable with that reported for adalimumab (0.49%).

The rates of serious infections were 2% in the tofacitinib phase III studies, and 2.9% in the tofacitinib long-term extensions, compared with 1.5% for adalimumab. There was some indication in the long-term extension data that the higher dose was associated with more serious infections than was the lower dose. Whether tofacitinib was given as monotherapy or with background DMARDs did not change the infection rate. Opportunistic infections, including tuberculosis, were uncommon.

In the second analysis, based on data from the long-term extension studies and reported by Dr. Jürgen Wollenhaupt of the University of Hamburg (Germany), there were some adverse events to "keep an eye out for," commented Dr. Bergman. This report represented data on 3,227 patients who were treated for a total duration of 3,118 patient-years. Serious adverse events were reported in 10.5% of patients. Confirmed increases in creatinine (defined as greater than 33% from baseline) were found in 12.2% of patients. Decreased hemoglobin levels (greater than or equal to 2 g/dL or less than 8) were found in 2.5% of patients, and raised aminotransferase levels (defined as greater than three times the upper limit of normal) were found in 1.7% (alanine) and 1.1% (aspartate) of patients. A 15% persistent rise across all doses was seen in total cholesterol. Diarrhea may also be a problem for some patients.

Dr. Bergman serves as a consultant to Pfizer.

NEW YORK – Among new medications under development for rheumatoid arthritis, oral Janus kinase inhibitors appear to be close to coming to market and have strong supportive clinical data, according to Dr. Martin Jan Bergman at a course sponsored by New York University.

Unlike most drugs for RA that affect extracellular cytokines, oral JAK inhibitors are small molecules that act to disrupt one of the intracellular signal pathways used by some cytokines to regulate immune and regulatory responses. Of this family of drugs, Pfizer’s tofacitinib primarily targets JAK3 (the JAK protein kinase that is most associated with inflammation), although it also overlaps to JAK1 and JAK2.

On Dec. 20, Pfizer announced that the Food and Drug Administration has accepted a New Drug Application for tofacitinib, formerly known as tasocitinib. About 1 month earlier, the European Medicines Agency had taken similar action, according to Pfizer.

According to Pfizer, nearly 5,000 patients with RA have undergone treatment in clinical trials of tofacitinib held at more than 350 sites in 35 countries worldwide. The data come primarily from the ORAL (Oral Rheumatoid Arthritis Phase III) trials, comprising five studies for which the data necessary for registration are complete, and one ongoing phase III trial. Two long-term, open-label extension studies are also ongoing.

During his presentation, Dr. Bergman reviewed data presented in 2001 at the annual European Congress of Rheumatology by Dr. Joel M. Kremer, head of the division of rheumatology at Albany (N.Y.) Medical College. Those data concerned the effects of tofacitinib in patients whose active RA had not responded to therapy with DMARDs (disease-modifying antirheumatic drugs). Patients received tofacitinib in doses of either 5 mg or 10 mg, in combination with background DMARDs. In this double-blind, placebo-controlled, randomized study of 792 patients, any patient in the placebo group who had not met the target efficacy response by 3 months was switched to tofacitinib 5 mg or 10 mg. All remaining placebo-treated patients were switched to tofacitinib by 6 months. At 6 months, 52.7% in those treated with tofacitinib 5 mg achieved ACR 20 (defined as 20% improvement on an American College of Rheumatology evaluation scale), as did 58.3% in those treated at the 10-mg dose, a response significantly greater than the placebo group. "Now we are starting to see levels that we see with [tumor necrosis factor] inhibitors," said Dr. Bergman of Drexel University in Philadelphia.

Dr. Kremer also found significant improvement on the DAS28-4 (ESR) – that is, the Disease Activity Score including a 28-joint count and the erythrocyte sedimentation rate – less than 2.6 for both doses of tofacitinib, as well as on the HAQ-DI (Health Assessment Questionnaire–Disability Index). "The minimally clinically important (MCI) difference for the HAQ-DI is 0.21 or 0.23; patients on tofacitinib had double the MCI improvement," noted Dr. Bergman, referring to the change of –0.46 for the 5-mg dose and –0.56 for the 10-mg dose (P less than .001, compared with placebo, for both differences). "What we see is very reassuring."

Dr. Bergman then highlighted some of data included in nine abstracts presented on tofacitinib at the 2011 annual meeting of the American College of Rheumatology. Dr. Roy M. Fleischmann of the University of Texas Southwestern Medical Center, Dallas, addressed the question of whether tofacitinib’s efficacy and safety hold up against the standard of care, such as a tumor necrosis factor (TNF) inhibitor (Arthritis Rheum. 2011;63[suppl.]:S153; abstract 408). In this 12-month trial, 717 patients were randomized to tofacitinib (5 mg or 10 mg twice daily), adalimumab (40-mg subcutaneous injections every 2 weeks), or placebo. "This was not a head-to-head trial, but rather comparability vs. placebo," commented Dr. Bergman. The results showed that tofacitinib 5 mg and 10 mg, as well as adalimumab, were statistically superior to placebo for all primary efficacy end points, and efficacy results for tofacitinib and adalimumab were numerically similar. "The ACR 20 responses (tofacitinib 5 mg, 51.5%; tofacitinib 10 mg, 52.6%; adalimumab, 47.2%) are very robust and comparable to the responses we see [with anti-TNFs] all the time," he added.

Tofacitinib also holds promise as a rescue therapy for RA patients with inadequate response to TNF inhibitors, as suggested by the results of a study by Dr. Gerd-Rüdiger Burmester of Charité Medical University Berlin (Arthritis Rheum. 2011;63[suppl.]:S279; abstract 718). In this 6-month study of 399 patients who were randomized to 5 mg or 10 mg of tofacitinib or placebo (or who were first treated with placebo and then given tofacitinib), rapid, significant and clinically meaningful improvements were noted in the signs and symptoms of RA (according to ACR 20/50/70 scores), physical functioning (per HAQ-DI scores) and disease activity (per DAS28-4 [ESR] scores less than 2.6). After looking at the ACR responses of the group that was initially given placebo and then 5-mg tofacitinib, Dr. Bergman commented that the 6-month ACR 20/50/70 responses (45.5, 28.79, and 10.6, respectively) were "identical to what we see with all of the rescue therapies currently available."

Interim results of a 24-month study regarding the effect of tofacitinib on radiographic progression were reported by Dr. Désirée van der Heijde of the department of rheumatology at Leiden (the Netherlands) University Medical Center (Arthritis Rheum. 2011;63[suppl.]:S1017-8; abstract 2592). The study included 797 patients with active RA who had a history of inadequate response to methotrexate and were on a stable dose of methotrexate. After 6 months of treatment, the mean change in the mTSS (modified Total Sharp Score) for tofacitinib 10 mg twice daily was 0.06, which was significantly lower (P less than .05) than placebo (mTSS, 0.47), indicating reduced progression of structural damage. The difference was not statistically significant for the 5-mg tofacitinib dose, in which the mTSS was 0.12.

In reviewing Dr. van der Heijde’s findings, Dr. Bergman questioned whether even a mean change of mTSS of 0.47 – on a scale of 0-400 – was clinically meaningful. At 12 months, the proportion of patients with no radiographic progression or no new erosions was greater in both tofacitinib groups, compared with placebo. "I don’t think we should make too much of these results, but I think the findings are reassuring that this oral medication has effects similar to the anti-TNFs," commented Dr. Bergman.

According to Dr. Bergman, more safety data are available for tofacitinib than for any other RA drug currently on the market, given its stage of development, especially as measured by patient-years. Two abstracts at the ACR annual meeting reported on long-term safety data, one summarizing pooled data from five randomized, double-blind, phase III studies, and two long-term, open-label extension studies (Arthritis Rheum. 2011;63[suppl.]:S153; abstract 409) and the other just from the same two long-term, open-label extension studies (Arthritis Rheum. 2011;63[suppl.]:S152-3; abstract 407). The former was an analysis by Dr. Stanley B. Cohen, a rheumatologist at the University of Texas, Dallas. It included 3,030 RA patients from the phase III trials and 3,227 from the long-term extensions, resulting in approximately 2,000 and 3,000 patient-years of exposure to tofacitinib. In the phase III studies, there were 12 deaths, with a death rate of 0.40% with tofacitinib (5 deaths caused by infections, and 2 with cardiovascular causes), and 8 deaths in the long-term extensions (3 from infections, and 1 with a cardiovascular cause), with a death rate of 0.62%; the rate for placebo was 0.15%. This rate was comparable with that reported for adalimumab (0.49%).

The rates of serious infections were 2% in the tofacitinib phase III studies, and 2.9% in the tofacitinib long-term extensions, compared with 1.5% for adalimumab. There was some indication in the long-term extension data that the higher dose was associated with more serious infections than was the lower dose. Whether tofacitinib was given as monotherapy or with background DMARDs did not change the infection rate. Opportunistic infections, including tuberculosis, were uncommon.

In the second analysis, based on data from the long-term extension studies and reported by Dr. Jürgen Wollenhaupt of the University of Hamburg (Germany), there were some adverse events to "keep an eye out for," commented Dr. Bergman. This report represented data on 3,227 patients who were treated for a total duration of 3,118 patient-years. Serious adverse events were reported in 10.5% of patients. Confirmed increases in creatinine (defined as greater than 33% from baseline) were found in 12.2% of patients. Decreased hemoglobin levels (greater than or equal to 2 g/dL or less than 8) were found in 2.5% of patients, and raised aminotransferase levels (defined as greater than three times the upper limit of normal) were found in 1.7% (alanine) and 1.1% (aspartate) of patients. A 15% persistent rise across all doses was seen in total cholesterol. Diarrhea may also be a problem for some patients.

Dr. Bergman serves as a consultant to Pfizer.

Lyme disease can create confusion for clinicians, especially when patients think it is causing their chronic, nonspecific symptoms, said Dr. Eugene Shapiro.

Patients with genuine Lyme disease may indeed have nonspecific symptoms, but – given that the disease does not cause chronic, nonspecific symptoms in the absence of objective signs of the illness – patients must also have an objective sign of Lyme disease, he explained.

Lyme disease can be classified into the following three categories:

• Early localized disease. This is "simply erythema migrans," said Dr. Shapiro, professor of pediatrics and of epidemiology and public health at Yale University, New Haven, Conn. It starts at the site of the tick bite, and expands for a few weeks if left untreated. Many people associate Lyme disease with a bull’s-eye, but it is more common to see uniform erythema, he said. "Don’t think that it is not erythema migrans just because there is no target lesion." Also, it is typical for the area of erythema not to be perfectly round, he added.

• Early disseminated disease. Signs of Lyme disease at this stage include multiple erythema migrans, symptoms of a flulike illness, aseptic meningitis, neuritis, and carditis. Meningitis is relatively uncommon in cases of Lyme disease, but it does occur, Dr. Shapiro noted. Neuritis (seventh-nerve palsy) is more common, but it is unaffected by treatment and usually resolves, he said.

• Late Lyme disease. Late disease is characterized by arthritis, and more than 90% of those cases of arthritis involve the knee, Dr. Shapiro said. The arthritis may be monoarticular or pauciarticular, and the duration of the arthritis varies, but it usually resolves with treatment, he said.

The question of "chronic" Lyme disease poses a different conundrum for clinicians. Although medically unexplained symptoms are common in these patients, most who complain of "chronic" Lyme disease have no evidence of ever having had the disease, based on history or serologic tests, he said. "We doctors are very good at treating diseases, but we are very poor at managing symptoms without a diagnosis," he added. His advice for managing such patients is to focus on treating the symptoms with a combination of counseling, increased exercise, improved sleep, cognitive-behavioral therapy, and in some cases, medication.

"Associated pathology is rare and rarely missed, whereas psychiatric diagnoses are common and often missed" in these patients, he said.

When it comes to prevention, be selective in ordering serologic tests, Dr. Shapiro emphasized. "Positive serologic test results without objective signs are very likely false-positive results," he said.

Dr. Shapiro made his remarks in Cambridge, Mass., at a conference on pediatric infectious diseases that was sponsored by Boston University, Pediatric News, and Family Practice News. Pediatric News and Family Practice News are owned by Elsevier. He disclosed that he is the official media spokesperson on Lyme disease for the Infectious Diseases Society of America.

Lyme disease can create confusion for clinicians, especially when patients think it is causing their chronic, nonspecific symptoms, said Dr. Eugene Shapiro.

Patients with genuine Lyme disease may indeed have nonspecific symptoms, but – given that the disease does not cause chronic, nonspecific symptoms in the absence of objective signs of the illness – patients must also have an objective sign of Lyme disease, he explained.

Lyme disease can be classified into the following three categories:

• Early localized disease. This is "simply erythema migrans," said Dr. Shapiro, professor of pediatrics and of epidemiology and public health at Yale University, New Haven, Conn. It starts at the site of the tick bite, and expands for a few weeks if left untreated. Many people associate Lyme disease with a bull’s-eye, but it is more common to see uniform erythema, he said. "Don’t think that it is not erythema migrans just because there is no target lesion." Also, it is typical for the area of erythema not to be perfectly round, he added.

• Early disseminated disease. Signs of Lyme disease at this stage include multiple erythema migrans, symptoms of a flulike illness, aseptic meningitis, neuritis, and carditis. Meningitis is relatively uncommon in cases of Lyme disease, but it does occur, Dr. Shapiro noted. Neuritis (seventh-nerve palsy) is more common, but it is unaffected by treatment and usually resolves, he said.

• Late Lyme disease. Late disease is characterized by arthritis, and more than 90% of those cases of arthritis involve the knee, Dr. Shapiro said. The arthritis may be monoarticular or pauciarticular, and the duration of the arthritis varies, but it usually resolves with treatment, he said.

The question of "chronic" Lyme disease poses a different conundrum for clinicians. Although medically unexplained symptoms are common in these patients, most who complain of "chronic" Lyme disease have no evidence of ever having had the disease, based on history or serologic tests, he said. "We doctors are very good at treating diseases, but we are very poor at managing symptoms without a diagnosis," he added. His advice for managing such patients is to focus on treating the symptoms with a combination of counseling, increased exercise, improved sleep, cognitive-behavioral therapy, and in some cases, medication.

"Associated pathology is rare and rarely missed, whereas psychiatric diagnoses are common and often missed" in these patients, he said.

When it comes to prevention, be selective in ordering serologic tests, Dr. Shapiro emphasized. "Positive serologic test results without objective signs are very likely false-positive results," he said.

Dr. Shapiro made his remarks in Cambridge, Mass., at a conference on pediatric infectious diseases that was sponsored by Boston University, Pediatric News, and Family Practice News. Pediatric News and Family Practice News are owned by Elsevier. He disclosed that he is the official media spokesperson on Lyme disease for the Infectious Diseases Society of America.

Lyme disease can create confusion for clinicians, especially when patients think it is causing their chronic, nonspecific symptoms, said Dr. Eugene Shapiro.

Patients with genuine Lyme disease may indeed have nonspecific symptoms, but – given that the disease does not cause chronic, nonspecific symptoms in the absence of objective signs of the illness – patients must also have an objective sign of Lyme disease, he explained.

Lyme disease can be classified into the following three categories:

• Early localized disease. This is "simply erythema migrans," said Dr. Shapiro, professor of pediatrics and of epidemiology and public health at Yale University, New Haven, Conn. It starts at the site of the tick bite, and expands for a few weeks if left untreated. Many people associate Lyme disease with a bull’s-eye, but it is more common to see uniform erythema, he said. "Don’t think that it is not erythema migrans just because there is no target lesion." Also, it is typical for the area of erythema not to be perfectly round, he added.

• Early disseminated disease. Signs of Lyme disease at this stage include multiple erythema migrans, symptoms of a flulike illness, aseptic meningitis, neuritis, and carditis. Meningitis is relatively uncommon in cases of Lyme disease, but it does occur, Dr. Shapiro noted. Neuritis (seventh-nerve palsy) is more common, but it is unaffected by treatment and usually resolves, he said.

• Late Lyme disease. Late disease is characterized by arthritis, and more than 90% of those cases of arthritis involve the knee, Dr. Shapiro said. The arthritis may be monoarticular or pauciarticular, and the duration of the arthritis varies, but it usually resolves with treatment, he said.

The question of "chronic" Lyme disease poses a different conundrum for clinicians. Although medically unexplained symptoms are common in these patients, most who complain of "chronic" Lyme disease have no evidence of ever having had the disease, based on history or serologic tests, he said. "We doctors are very good at treating diseases, but we are very poor at managing symptoms without a diagnosis," he added. His advice for managing such patients is to focus on treating the symptoms with a combination of counseling, increased exercise, improved sleep, cognitive-behavioral therapy, and in some cases, medication.

"Associated pathology is rare and rarely missed, whereas psychiatric diagnoses are common and often missed" in these patients, he said.

When it comes to prevention, be selective in ordering serologic tests, Dr. Shapiro emphasized. "Positive serologic test results without objective signs are very likely false-positive results," he said.

Dr. Shapiro made his remarks in Cambridge, Mass., at a conference on pediatric infectious diseases that was sponsored by Boston University, Pediatric News, and Family Practice News. Pediatric News and Family Practice News are owned by Elsevier. He disclosed that he is the official media spokesperson on Lyme disease for the Infectious Diseases Society of America.

LISBON – Switching to adalimumab in psoriasis patients who are not responding adequately to etanercept is significantly more cost effective than escalating the etanercept dose, an analysis has shown.

During the first 6 months following the decision to either switch or escalate, 372 etaner cept (Enbrel) dose escalators incurred an adjusted average of $2,451 more in incremental total health care costs than the $12,943 average in 728 patients who instead switched to adalimumab (Humira), Dr. Kim A. Papp reported at the annual congress of the European Academy of Dermatology and Venereology.

Driving the markedly higher total costs in the etanercept dose escalation group was their significantly greater utilization of both inpatient and outpatient services, including urgent care. Also, psoriasis drug costs, which accounted for 75% of total health care costs, were significantly lower in the group that switched to adalimumab. The cost of adalimumab over the course of 6 months averaged an adjusted $1,573 less per patient than etanercept therapy, according to Dr. Papp, director of research at Probity Medical Research in Waterloo, Ont.

Subjects for this analysis were drawn from the MarketScan and Ingenix Impact National Managed Care databases. All participants were etanercept-treated psoriasis patients with full health care utilization and cost data accessible for the 6 months immediately before the escalate or switch decision and for 6 months afterward.

The two groups had nearly identical total health care costs during the baseline first 6 months: an average of $11,264 in patients prior to etanercept dose escalation, compared with $11,628 in those who went on to switch to adalimumab. The two groups were similar in age, sex, and comorbidities. However, the switchers appeared to have more severe psoriasis. They had a greater prevalence of psoriatic arthritis. Moreover, during the baseline period, they had significantly more outpatient visits, and 41% of them used antimicrobial medications, compared with 33% in the dose escalation group. These potential confounders were adjusted for in the analysis.

This switch or escalate decision point is a common but underappreciated aspect of etanercept therapy. Prior studies have established that 30%-50% of psoriasis patients placed on etanercept require a dosing increase during the first year of therapy, according to Dr. Papp.

This study was funded by Abbott Laboratories. Dr. Papp disclosed that he serves as an adviser to Abbott as well as numerous other pharmaceutical companies funding psoriasis research.

LISBON – Switching to adalimumab in psoriasis patients who are not responding adequately to etanercept is significantly more cost effective than escalating the etanercept dose, an analysis has shown.

During the first 6 months following the decision to either switch or escalate, 372 etaner cept (Enbrel) dose escalators incurred an adjusted average of $2,451 more in incremental total health care costs than the $12,943 average in 728 patients who instead switched to adalimumab (Humira), Dr. Kim A. Papp reported at the annual congress of the European Academy of Dermatology and Venereology.

Driving the markedly higher total costs in the etanercept dose escalation group was their significantly greater utilization of both inpatient and outpatient services, including urgent care. Also, psoriasis drug costs, which accounted for 75% of total health care costs, were significantly lower in the group that switched to adalimumab. The cost of adalimumab over the course of 6 months averaged an adjusted $1,573 less per patient than etanercept therapy, according to Dr. Papp, director of research at Probity Medical Research in Waterloo, Ont.

Subjects for this analysis were drawn from the MarketScan and Ingenix Impact National Managed Care databases. All participants were etanercept-treated psoriasis patients with full health care utilization and cost data accessible for the 6 months immediately before the escalate or switch decision and for 6 months afterward.

The two groups had nearly identical total health care costs during the baseline first 6 months: an average of $11,264 in patients prior to etanercept dose escalation, compared with $11,628 in those who went on to switch to adalimumab. The two groups were similar in age, sex, and comorbidities. However, the switchers appeared to have more severe psoriasis. They had a greater prevalence of psoriatic arthritis. Moreover, during the baseline period, they had significantly more outpatient visits, and 41% of them used antimicrobial medications, compared with 33% in the dose escalation group. These potential confounders were adjusted for in the analysis.

This switch or escalate decision point is a common but underappreciated aspect of etanercept therapy. Prior studies have established that 30%-50% of psoriasis patients placed on etanercept require a dosing increase during the first year of therapy, according to Dr. Papp.

This study was funded by Abbott Laboratories. Dr. Papp disclosed that he serves as an adviser to Abbott as well as numerous other pharmaceutical companies funding psoriasis research.

LISBON – Switching to adalimumab in psoriasis patients who are not responding adequately to etanercept is significantly more cost effective than escalating the etanercept dose, an analysis has shown.

During the first 6 months following the decision to either switch or escalate, 372 etaner cept (Enbrel) dose escalators incurred an adjusted average of $2,451 more in incremental total health care costs than the $12,943 average in 728 patients who instead switched to adalimumab (Humira), Dr. Kim A. Papp reported at the annual congress of the European Academy of Dermatology and Venereology.

Driving the markedly higher total costs in the etanercept dose escalation group was their significantly greater utilization of both inpatient and outpatient services, including urgent care. Also, psoriasis drug costs, which accounted for 75% of total health care costs, were significantly lower in the group that switched to adalimumab. The cost of adalimumab over the course of 6 months averaged an adjusted $1,573 less per patient than etanercept therapy, according to Dr. Papp, director of research at Probity Medical Research in Waterloo, Ont.

Subjects for this analysis were drawn from the MarketScan and Ingenix Impact National Managed Care databases. All participants were etanercept-treated psoriasis patients with full health care utilization and cost data accessible for the 6 months immediately before the escalate or switch decision and for 6 months afterward.

The two groups had nearly identical total health care costs during the baseline first 6 months: an average of $11,264 in patients prior to etanercept dose escalation, compared with $11,628 in those who went on to switch to adalimumab. The two groups were similar in age, sex, and comorbidities. However, the switchers appeared to have more severe psoriasis. They had a greater prevalence of psoriatic arthritis. Moreover, during the baseline period, they had significantly more outpatient visits, and 41% of them used antimicrobial medications, compared with 33% in the dose escalation group. These potential confounders were adjusted for in the analysis.

This switch or escalate decision point is a common but underappreciated aspect of etanercept therapy. Prior studies have established that 30%-50% of psoriasis patients placed on etanercept require a dosing increase during the first year of therapy, according to Dr. Papp.

This study was funded by Abbott Laboratories. Dr. Papp disclosed that he serves as an adviser to Abbott as well as numerous other pharmaceutical companies funding psoriasis research.

Administration of a proton pump inhibitor with intravenous methotrexate may result in elevated serum levels of methotrexate, with toxic consequences, according to a statement issued on Dec. 21 by the Food and Drug Administration.

Case reports and published pharmacokinetic studies "suggest" that concomitant use of proton pump inhibitors (PPIs) with methotrexate, primarily high dose methotrexate, "may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities," the statement says.

In two cases, elimination of methotrexate was delayed when it was administered with a PPI but not when it was administered with ranitidine, the statement says. However, no formal drug interaction studies of methotrexate and ranitidine have been conducted, the statement adds. Ranitidine, a histamine H2-receptor antagonist used for similar indications as PPIs, is marketed as Zantac and is available in generic formulations.

The FDA is recommending that clinicians "use caution when administering high-dose methotrexate to patients receiving proton pump inhibitor therapy," and this information has been added to the warnings section of the label for methotrexate.

Methotrexate, classified as an antimetabolite, is approved to treat neoplastic diseases, severe psoriasis, and rheumatoid arthritis. PPIs are widely used drugs used to treat several conditions, including gastroesophageal reflux disease. The PPIs available in the United States include omeprazole (Prilosec), esomeprazole (Nexium), lansoprazole (Prevacid), and pantoprazole (Protonix), as well as several generic and over-the-counter formulations. The FDA statement did not say that the warning is being added to the PPI labels.

Serious adverse events associated with these and other drugs should be reported to the FDA’s MedWatch program at 800-332-1088.

Administration of a proton pump inhibitor with intravenous methotrexate may result in elevated serum levels of methotrexate, with toxic consequences, according to a statement issued on Dec. 21 by the Food and Drug Administration.

Case reports and published pharmacokinetic studies "suggest" that concomitant use of proton pump inhibitors (PPIs) with methotrexate, primarily high dose methotrexate, "may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities," the statement says.

In two cases, elimination of methotrexate was delayed when it was administered with a PPI but not when it was administered with ranitidine, the statement says. However, no formal drug interaction studies of methotrexate and ranitidine have been conducted, the statement adds. Ranitidine, a histamine H2-receptor antagonist used for similar indications as PPIs, is marketed as Zantac and is available in generic formulations.

The FDA is recommending that clinicians "use caution when administering high-dose methotrexate to patients receiving proton pump inhibitor therapy," and this information has been added to the warnings section of the label for methotrexate.

Methotrexate, classified as an antimetabolite, is approved to treat neoplastic diseases, severe psoriasis, and rheumatoid arthritis. PPIs are widely used drugs used to treat several conditions, including gastroesophageal reflux disease. The PPIs available in the United States include omeprazole (Prilosec), esomeprazole (Nexium), lansoprazole (Prevacid), and pantoprazole (Protonix), as well as several generic and over-the-counter formulations. The FDA statement did not say that the warning is being added to the PPI labels.

Serious adverse events associated with these and other drugs should be reported to the FDA’s MedWatch program at 800-332-1088.

Administration of a proton pump inhibitor with intravenous methotrexate may result in elevated serum levels of methotrexate, with toxic consequences, according to a statement issued on Dec. 21 by the Food and Drug Administration.

Case reports and published pharmacokinetic studies "suggest" that concomitant use of proton pump inhibitors (PPIs) with methotrexate, primarily high dose methotrexate, "may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities," the statement says.

In two cases, elimination of methotrexate was delayed when it was administered with a PPI but not when it was administered with ranitidine, the statement says. However, no formal drug interaction studies of methotrexate and ranitidine have been conducted, the statement adds. Ranitidine, a histamine H2-receptor antagonist used for similar indications as PPIs, is marketed as Zantac and is available in generic formulations.

The FDA is recommending that clinicians "use caution when administering high-dose methotrexate to patients receiving proton pump inhibitor therapy," and this information has been added to the warnings section of the label for methotrexate.

Methotrexate, classified as an antimetabolite, is approved to treat neoplastic diseases, severe psoriasis, and rheumatoid arthritis. PPIs are widely used drugs used to treat several conditions, including gastroesophageal reflux disease. The PPIs available in the United States include omeprazole (Prilosec), esomeprazole (Nexium), lansoprazole (Prevacid), and pantoprazole (Protonix), as well as several generic and over-the-counter formulations. The FDA statement did not say that the warning is being added to the PPI labels.

Serious adverse events associated with these and other drugs should be reported to the FDA’s MedWatch program at 800-332-1088.

CHICAGO – The novel anti–tumor necrosis factor nanobody ATN-103 looks as if it will be moving on to phase III trials, based on the good efficacy and safety results of a phase IIA trial of more than 250 patients with rheumatoid arthritis.

"The 80-mg, every-4-weeks regimen was the one [dosage] that was consistently improved over placebo by ACR 20" (the American College of Rheumatology evaluation scale that reflects a 20% improvement in specified parameters), Dr. Roy M. Fleischmann said at the American College of Rheumatology annual meeting. In addition, this dosage group comprised the only patients to achieve significantly better responses on the ACR 50 and the ACR 70 criteria than was achieved by those taking placebo.

A nanobody is the smallest functional fragment of a naturally occurring, single-chain antibody, and ATN-103 (ozoralizumab) is just one-quarter the size of conventional TNF-blockers, Dr. Fleischmann noted. As a humanized bispecific nanobody, ATN-103 contains two human TNF-binding domains that are linked to a human serum albumin–binding domain to extend half-life.

The researchers conducted a double-blind, placebo-controlled, phase IIA proof-of-concept study that included 253 patients in three treatment groups, with roughly 40 patients at each dosage level. The 4-week dosing group received the active drug (a subcutaneous injection of 10 mg, 30 mg, or 80 mg) on day 1 of weeks 4, 8, and 12. The 8-week dosing group received either 10 mg or 80 mg of the drug on day 1 of each 8-week period. Those in the placebo group received a placebo injection on day 1 of weeks 4, 8, and 12.

All of the patients had active RA (defined as at least six swollen and at least six tender joints) at the time of screening and at baseline, despite having been treated with methotrexate for at least 12 weeks. To qualify for the study, they had to meet the 1987 revised criteria for RA at least 24 weeks prior to screening, to be within ACR functional class I-III, and to have a C-reactive protein level of at least 8 mg/L. In addition, their methotrexate dose (7.5-25 mg) and route of administration had to be stable for at least 6 weeks prior to baseline. The patients were stratified by prior TNF-inhibitor use; two-thirds of them were naive to TNF-blockers.

The primary outcome of this study was ACR 20 at 16 weeks. Secondary end points were improvements over placebo in clinical scores, DAS28 (Disease Activity Score based on a 28-joint count), ACR 50, ACR 70, and EULAR responses at week 16.

The ACR criteria are used to evaluate improvement in tender or swollen joint counts, as well as improvement in three of the following five parameters: acute phase reactant, patient assessment, physician assessment, pain scale, and disability/functional questionnaire scores. The EULAR response includes not only change in disease activity but also current disease activity.

"The safety profile looked relatively clean," said Dr. Fleischmann of the Metroplex Clinical Research Center in Dallas. Of 43 patients in the 80-mg, every-4-weeks group, there were 23 adverse reactions, of which infections were the most common at 19% – a safety profile similar to that of other anti-TNFs. One patient did withdraw from this group because of adverse events (AEs), but there were no deaths, no dose-limiting toxicities, and no clinically significant increases in AEs or serious AEs with increasing dose. Overall, 13 patients reported 17 serious AEs, of which respiratory tract infections and disorders were the most common.

The trial was sponsored by Pfizer, and all of the authors noted significant financial relationships with the company.

CHICAGO – The novel anti–tumor necrosis factor nanobody ATN-103 looks as if it will be moving on to phase III trials, based on the good efficacy and safety results of a phase IIA trial of more than 250 patients with rheumatoid arthritis.

"The 80-mg, every-4-weeks regimen was the one [dosage] that was consistently improved over placebo by ACR 20" (the American College of Rheumatology evaluation scale that reflects a 20% improvement in specified parameters), Dr. Roy M. Fleischmann said at the American College of Rheumatology annual meeting. In addition, this dosage group comprised the only patients to achieve significantly better responses on the ACR 50 and the ACR 70 criteria than was achieved by those taking placebo.

A nanobody is the smallest functional fragment of a naturally occurring, single-chain antibody, and ATN-103 (ozoralizumab) is just one-quarter the size of conventional TNF-blockers, Dr. Fleischmann noted. As a humanized bispecific nanobody, ATN-103 contains two human TNF-binding domains that are linked to a human serum albumin–binding domain to extend half-life.

The researchers conducted a double-blind, placebo-controlled, phase IIA proof-of-concept study that included 253 patients in three treatment groups, with roughly 40 patients at each dosage level. The 4-week dosing group received the active drug (a subcutaneous injection of 10 mg, 30 mg, or 80 mg) on day 1 of weeks 4, 8, and 12. The 8-week dosing group received either 10 mg or 80 mg of the drug on day 1 of each 8-week period. Those in the placebo group received a placebo injection on day 1 of weeks 4, 8, and 12.

All of the patients had active RA (defined as at least six swollen and at least six tender joints) at the time of screening and at baseline, despite having been treated with methotrexate for at least 12 weeks. To qualify for the study, they had to meet the 1987 revised criteria for RA at least 24 weeks prior to screening, to be within ACR functional class I-III, and to have a C-reactive protein level of at least 8 mg/L. In addition, their methotrexate dose (7.5-25 mg) and route of administration had to be stable for at least 6 weeks prior to baseline. The patients were stratified by prior TNF-inhibitor use; two-thirds of them were naive to TNF-blockers.

The primary outcome of this study was ACR 20 at 16 weeks. Secondary end points were improvements over placebo in clinical scores, DAS28 (Disease Activity Score based on a 28-joint count), ACR 50, ACR 70, and EULAR responses at week 16.

The ACR criteria are used to evaluate improvement in tender or swollen joint counts, as well as improvement in three of the following five parameters: acute phase reactant, patient assessment, physician assessment, pain scale, and disability/functional questionnaire scores. The EULAR response includes not only change in disease activity but also current disease activity.

"The safety profile looked relatively clean," said Dr. Fleischmann of the Metroplex Clinical Research Center in Dallas. Of 43 patients in the 80-mg, every-4-weeks group, there were 23 adverse reactions, of which infections were the most common at 19% – a safety profile similar to that of other anti-TNFs. One patient did withdraw from this group because of adverse events (AEs), but there were no deaths, no dose-limiting toxicities, and no clinically significant increases in AEs or serious AEs with increasing dose. Overall, 13 patients reported 17 serious AEs, of which respiratory tract infections and disorders were the most common.

The trial was sponsored by Pfizer, and all of the authors noted significant financial relationships with the company.

CHICAGO – The novel anti–tumor necrosis factor nanobody ATN-103 looks as if it will be moving on to phase III trials, based on the good efficacy and safety results of a phase IIA trial of more than 250 patients with rheumatoid arthritis.

"The 80-mg, every-4-weeks regimen was the one [dosage] that was consistently improved over placebo by ACR 20" (the American College of Rheumatology evaluation scale that reflects a 20% improvement in specified parameters), Dr. Roy M. Fleischmann said at the American College of Rheumatology annual meeting. In addition, this dosage group comprised the only patients to achieve significantly better responses on the ACR 50 and the ACR 70 criteria than was achieved by those taking placebo.

A nanobody is the smallest functional fragment of a naturally occurring, single-chain antibody, and ATN-103 (ozoralizumab) is just one-quarter the size of conventional TNF-blockers, Dr. Fleischmann noted. As a humanized bispecific nanobody, ATN-103 contains two human TNF-binding domains that are linked to a human serum albumin–binding domain to extend half-life.

The researchers conducted a double-blind, placebo-controlled, phase IIA proof-of-concept study that included 253 patients in three treatment groups, with roughly 40 patients at each dosage level. The 4-week dosing group received the active drug (a subcutaneous injection of 10 mg, 30 mg, or 80 mg) on day 1 of weeks 4, 8, and 12. The 8-week dosing group received either 10 mg or 80 mg of the drug on day 1 of each 8-week period. Those in the placebo group received a placebo injection on day 1 of weeks 4, 8, and 12.

All of the patients had active RA (defined as at least six swollen and at least six tender joints) at the time of screening and at baseline, despite having been treated with methotrexate for at least 12 weeks. To qualify for the study, they had to meet the 1987 revised criteria for RA at least 24 weeks prior to screening, to be within ACR functional class I-III, and to have a C-reactive protein level of at least 8 mg/L. In addition, their methotrexate dose (7.5-25 mg) and route of administration had to be stable for at least 6 weeks prior to baseline. The patients were stratified by prior TNF-inhibitor use; two-thirds of them were naive to TNF-blockers.

The primary outcome of this study was ACR 20 at 16 weeks. Secondary end points were improvements over placebo in clinical scores, DAS28 (Disease Activity Score based on a 28-joint count), ACR 50, ACR 70, and EULAR responses at week 16.

The ACR criteria are used to evaluate improvement in tender or swollen joint counts, as well as improvement in three of the following five parameters: acute phase reactant, patient assessment, physician assessment, pain scale, and disability/functional questionnaire scores. The EULAR response includes not only change in disease activity but also current disease activity.

"The safety profile looked relatively clean," said Dr. Fleischmann of the Metroplex Clinical Research Center in Dallas. Of 43 patients in the 80-mg, every-4-weeks group, there were 23 adverse reactions, of which infections were the most common at 19% – a safety profile similar to that of other anti-TNFs. One patient did withdraw from this group because of adverse events (AEs), but there were no deaths, no dose-limiting toxicities, and no clinically significant increases in AEs or serious AEs with increasing dose. Overall, 13 patients reported 17 serious AEs, of which respiratory tract infections and disorders were the most common.

The trial was sponsored by Pfizer, and all of the authors noted significant financial relationships with the company.

CHICAGO – A causal relationship between rheumatoid arthritis and periodontal disease has not been confirmed, but recent data support the concept of a bi-directional relationship between the two.

In fact, a number of investigators have attempted to characterize the relationship between rheumatoid arthritis (RA) and periodontal disease. While most research confirms that one exists, the strength and extent of that relationship remain unclear, Michele Ravenel, D.M.D., said at the annual meeting of the American College of Rheumatology.

"Periodontal disease and RA do share similar pathologic mechanisms, and the relationship appears to be bi-directional," Dr. Ravenel said. But in her own review of the literature, the only consistency she found was inconsistency, said Dr. Ravenel.

In one recent case-control study involving 57 RA patients and 52 healthy subjects, those with RA were found to have significantly greater odds of having periodontitis after adjusting for a number of variables including RA status, age, sex, alcohol use, and body mass index (J. Periodontol. 2008;79:979-86).

"Periodontal disease and RA do share similar pathologic mechanisms, and the relationship appears to be bi-directional," said Michele Ravenel, D.M.D.

And in another recent study, 65 RA patients all were found to have some form of periodontal disease, which was moderate or severe in most cases. However, rheumatoid factor levels were not found to have any influence on oral bacterial composition and/or concentration – or on severity of periodontal disease (J. Periodontol. 2011;82:1424-32).

In yet another study of patients with both moderate to severe RA and severe periodontal disease, outcomes were compared in 10 patients on no treatment, 10 on periodontal therapy, 10 on anti-TNF-alpha therapy, and 10 on both periodontal therapy and anti-TNF-alpha therapy (J. Periodontol. 2009;80:535-40). Patients who were receiving treatment for periodontal disease – either with or without anti-TNF-alpha therapy for their RA – experienced significantly greater improvements in both the periodontal disease and the RA, compared with those not on periodontal therapy, said Dr. Ravenel of the Medical University of South Carolina, Charleston.

As for the role of periodontal pathogens in RA, findings from two recent case-control studies showed that serum antibodies to known periodontal pathogens were found more frequently in those with RA and periodontal disease than in controls (MedGenMed. 2005;7:2;Clin. Exp. Rheumatol. 2006;24:656-63).

In a cross-sectional study, bacterial DNA of some of the more virulent periodontal pathogens, including Porphyromonas gingivalis, Tannerella forsythia, and Prevotella intermedia, were identified in synovial fluid of RA-affected joints (J. Clin. Periodontol. 2009;1004-10).

In another study, which was presented separately at the 2011 annual meeting of the ACR, Dr. Jose U. Scher reported on a potentially important role for "a single species-level operational taxonomic unit belonging to the genus Porphyromonas and homologous to P. gingivalis," which he said could explain the link between RA and periodontal disease.

The particular Porphyromonas species was significantly more prevalent and more abundant in 25 patients with new-onset, never-treated RA, compared with 27 patients with established disease, and 14 healthy controls. That species accounted for nearly 10% of the bacteria in the new-onset RA patients, compared with about 3% and 4% of the bacteria in control patients and patients with chronic established disease, respectively, said Dr. Scher, of New York University Hospital for Joint Diseases.

More than 90% of the patients with new-onset RA in the study had moderate to severe periodontal disease. The study findings showed that the oral microbiome in these patients – all of whom were anticitrullinated peptide antibody-positive – is distinct at disease onset and characterized by an abundance of the virulent Porphyromonas species.

Further identification of the species may provide new insight regarding the reported link between RA and periodontal disease, he concluded.

Additional research should include strict adherence to diagnostic criteria for both diseases, Dr. Ravenel said.

Dr. Ravenel and Dr. Scher both said they have no relevant disclosures.

CHICAGO – A causal relationship between rheumatoid arthritis and periodontal disease has not been confirmed, but recent data support the concept of a bi-directional relationship between the two.

In fact, a number of investigators have attempted to characterize the relationship between rheumatoid arthritis (RA) and periodontal disease. While most research confirms that one exists, the strength and extent of that relationship remain unclear, Michele Ravenel, D.M.D., said at the annual meeting of the American College of Rheumatology.

"Periodontal disease and RA do share similar pathologic mechanisms, and the relationship appears to be bi-directional," Dr. Ravenel said. But in her own review of the literature, the only consistency she found was inconsistency, said Dr. Ravenel.

In one recent case-control study involving 57 RA patients and 52 healthy subjects, those with RA were found to have significantly greater odds of having periodontitis after adjusting for a number of variables including RA status, age, sex, alcohol use, and body mass index (J. Periodontol. 2008;79:979-86).

"Periodontal disease and RA do share similar pathologic mechanisms, and the relationship appears to be bi-directional," said Michele Ravenel, D.M.D.

And in another recent study, 65 RA patients all were found to have some form of periodontal disease, which was moderate or severe in most cases. However, rheumatoid factor levels were not found to have any influence on oral bacterial composition and/or concentration – or on severity of periodontal disease (J. Periodontol. 2011;82:1424-32).

In yet another study of patients with both moderate to severe RA and severe periodontal disease, outcomes were compared in 10 patients on no treatment, 10 on periodontal therapy, 10 on anti-TNF-alpha therapy, and 10 on both periodontal therapy and anti-TNF-alpha therapy (J. Periodontol. 2009;80:535-40). Patients who were receiving treatment for periodontal disease – either with or without anti-TNF-alpha therapy for their RA – experienced significantly greater improvements in both the periodontal disease and the RA, compared with those not on periodontal therapy, said Dr. Ravenel of the Medical University of South Carolina, Charleston.

As for the role of periodontal pathogens in RA, findings from two recent case-control studies showed that serum antibodies to known periodontal pathogens were found more frequently in those with RA and periodontal disease than in controls (MedGenMed. 2005;7:2;Clin. Exp. Rheumatol. 2006;24:656-63).

In a cross-sectional study, bacterial DNA of some of the more virulent periodontal pathogens, including Porphyromonas gingivalis, Tannerella forsythia, and Prevotella intermedia, were identified in synovial fluid of RA-affected joints (J. Clin. Periodontol. 2009;1004-10).

In another study, which was presented separately at the 2011 annual meeting of the ACR, Dr. Jose U. Scher reported on a potentially important role for "a single species-level operational taxonomic unit belonging to the genus Porphyromonas and homologous to P. gingivalis," which he said could explain the link between RA and periodontal disease.

The particular Porphyromonas species was significantly more prevalent and more abundant in 25 patients with new-onset, never-treated RA, compared with 27 patients with established disease, and 14 healthy controls. That species accounted for nearly 10% of the bacteria in the new-onset RA patients, compared with about 3% and 4% of the bacteria in control patients and patients with chronic established disease, respectively, said Dr. Scher, of New York University Hospital for Joint Diseases.

More than 90% of the patients with new-onset RA in the study had moderate to severe periodontal disease. The study findings showed that the oral microbiome in these patients – all of whom were anticitrullinated peptide antibody-positive – is distinct at disease onset and characterized by an abundance of the virulent Porphyromonas species.

Further identification of the species may provide new insight regarding the reported link between RA and periodontal disease, he concluded.

Additional research should include strict adherence to diagnostic criteria for both diseases, Dr. Ravenel said.

Dr. Ravenel and Dr. Scher both said they have no relevant disclosures.

CHICAGO – A causal relationship between rheumatoid arthritis and periodontal disease has not been confirmed, but recent data support the concept of a bi-directional relationship between the two.

In fact, a number of investigators have attempted to characterize the relationship between rheumatoid arthritis (RA) and periodontal disease. While most research confirms that one exists, the strength and extent of that relationship remain unclear, Michele Ravenel, D.M.D., said at the annual meeting of the American College of Rheumatology.

"Periodontal disease and RA do share similar pathologic mechanisms, and the relationship appears to be bi-directional," Dr. Ravenel said. But in her own review of the literature, the only consistency she found was inconsistency, said Dr. Ravenel.

In one recent case-control study involving 57 RA patients and 52 healthy subjects, those with RA were found to have significantly greater odds of having periodontitis after adjusting for a number of variables including RA status, age, sex, alcohol use, and body mass index (J. Periodontol. 2008;79:979-86).

"Periodontal disease and RA do share similar pathologic mechanisms, and the relationship appears to be bi-directional," said Michele Ravenel, D.M.D.

And in another recent study, 65 RA patients all were found to have some form of periodontal disease, which was moderate or severe in most cases. However, rheumatoid factor levels were not found to have any influence on oral bacterial composition and/or concentration – or on severity of periodontal disease (J. Periodontol. 2011;82:1424-32).

In yet another study of patients with both moderate to severe RA and severe periodontal disease, outcomes were compared in 10 patients on no treatment, 10 on periodontal therapy, 10 on anti-TNF-alpha therapy, and 10 on both periodontal therapy and anti-TNF-alpha therapy (J. Periodontol. 2009;80:535-40). Patients who were receiving treatment for periodontal disease – either with or without anti-TNF-alpha therapy for their RA – experienced significantly greater improvements in both the periodontal disease and the RA, compared with those not on periodontal therapy, said Dr. Ravenel of the Medical University of South Carolina, Charleston.

As for the role of periodontal pathogens in RA, findings from two recent case-control studies showed that serum antibodies to known periodontal pathogens were found more frequently in those with RA and periodontal disease than in controls (MedGenMed. 2005;7:2;Clin. Exp. Rheumatol. 2006;24:656-63).

In a cross-sectional study, bacterial DNA of some of the more virulent periodontal pathogens, including Porphyromonas gingivalis, Tannerella forsythia, and Prevotella intermedia, were identified in synovial fluid of RA-affected joints (J. Clin. Periodontol. 2009;1004-10).

In another study, which was presented separately at the 2011 annual meeting of the ACR, Dr. Jose U. Scher reported on a potentially important role for "a single species-level operational taxonomic unit belonging to the genus Porphyromonas and homologous to P. gingivalis," which he said could explain the link between RA and periodontal disease.

The particular Porphyromonas species was significantly more prevalent and more abundant in 25 patients with new-onset, never-treated RA, compared with 27 patients with established disease, and 14 healthy controls. That species accounted for nearly 10% of the bacteria in the new-onset RA patients, compared with about 3% and 4% of the bacteria in control patients and patients with chronic established disease, respectively, said Dr. Scher, of New York University Hospital for Joint Diseases.

More than 90% of the patients with new-onset RA in the study had moderate to severe periodontal disease. The study findings showed that the oral microbiome in these patients – all of whom were anticitrullinated peptide antibody-positive – is distinct at disease onset and characterized by an abundance of the virulent Porphyromonas species.

Further identification of the species may provide new insight regarding the reported link between RA and periodontal disease, he concluded.

Additional research should include strict adherence to diagnostic criteria for both diseases, Dr. Ravenel said.

Dr. Ravenel and Dr. Scher both said they have no relevant disclosures.

CHICAGO – Metabolic syndrome is significantly more common in patients with psoriatic arthritis than in those with rheumatoid arthritis, based on data from nearly 2,000 adults.

Previous studies have suggested that metabolic syndrome is associated with "a state of chronic, low-grade inflammation," said Dr. Asena Bahce-Altuntas of Albert Einstein College of Medicine in New York.

"Since psoriatic arthritis [PsA] is characterized by inflammation of both skin and joints, we may be underestimating this cardiovascular risk in PsA," she said at the annual meeting of the American College of Rheumatology.

To compare the prevalence of metabolic syndrome in patients with PsA versus rheumatoid arthritis (RA), Dr. Bahce-Altuntas and her colleagues used data from the Consortium of Rheumatology Researchers of North America (CORRONA) registry, a prospective, observational cohort including 4,014 patients with PsA and 25,976 patients with RA in academic and private practices throughout the United States. Lipid profile data were available for 1,956 patients from the CORRONA registry: 294 with PsA and 1,662 with RA.

Overall, 27% of PsA patients met criteria for metabolic syndrome, compared with 19% of RA patients. In addition, several specific components of metabolic syndrome were significantly more common in PsA patients.

In particular, significantly more PsA patients than RA patients had triglycerides greater than 150 mg/dL (38% vs. 28%).

Significantly more PsA patients than RA patients were male (54% vs. 23%, respectively), and the mean age was significantly greater in RA patients than in PsA patients (62 years vs. 56 years, respectively). However, after age, sex, and ethnicity were controlled for, the odds of metabolic syndrome remained significantly higher for PsA patients (odds ratio, 1.44).

Metabolic syndrome was defined as a body mass index greater than 30 kg/m² and any two of the following criteria: triglycerides greater than 150 mg/dL, HDL less than 40 mg/dL for men or less than 50 mg/dL for women, a diagnosis of hypertension, or a diagnosis of diabetes.

In a subanalysis of obese patients (133 PsA patients and 654 RA patients with a BMI greater than 30), the prevalence of metabolic syndrome remained significantly higher in PsA patients (60%) than in RA patients (49%), as did the prevalence of patients with triglycerides greater than 150 mg/dL (51% vs. 39%).

The study was limited by the relatively small sample of PsA patients, and by the modified metabolic syndrome criteria that may have underestimated the prevalence of metabolic syndrome in both groups, said Dr. Bahce-Altuntas.

However, the results suggest that metabolic syndrome and its components are significantly more common in PsA than in RA. "High triglycerides appear to drive the estimated increase in risk of metabolic syndrome in PsA vs. RA," she noted.

The combination of skin and joint inflammation in PsA may contribute to the increased frequency of metabolic syndrome in these patients, but more research is needed, Dr. Bahce-Altuntas said.

Meanwhile, "more intensive interventions to modify these risk factors are warranted in PsA patients in order to reduce cardiovascular morbidity and mortality," she said.

The following companies have supported CORRONA through contracted subscriptions over the past 2 years: Abbott, Amgen, AstraZeneca, Bristol-Myers Squibb, Centocor, Genentech, Lilly, Pfizer, and Roche. Dr. Bahce-Altuntas had no financial conflicts to disclose.

CHICAGO – Metabolic syndrome is significantly more common in patients with psoriatic arthritis than in those with rheumatoid arthritis, based on data from nearly 2,000 adults.

Previous studies have suggested that metabolic syndrome is associated with "a state of chronic, low-grade inflammation," said Dr. Asena Bahce-Altuntas of Albert Einstein College of Medicine in New York.

"Since psoriatic arthritis [PsA] is characterized by inflammation of both skin and joints, we may be underestimating this cardiovascular risk in PsA," she said at the annual meeting of the American College of Rheumatology.

To compare the prevalence of metabolic syndrome in patients with PsA versus rheumatoid arthritis (RA), Dr. Bahce-Altuntas and her colleagues used data from the Consortium of Rheumatology Researchers of North America (CORRONA) registry, a prospective, observational cohort including 4,014 patients with PsA and 25,976 patients with RA in academic and private practices throughout the United States. Lipid profile data were available for 1,956 patients from the CORRONA registry: 294 with PsA and 1,662 with RA.

Overall, 27% of PsA patients met criteria for metabolic syndrome, compared with 19% of RA patients. In addition, several specific components of metabolic syndrome were significantly more common in PsA patients.

In particular, significantly more PsA patients than RA patients had triglycerides greater than 150 mg/dL (38% vs. 28%).

Significantly more PsA patients than RA patients were male (54% vs. 23%, respectively), and the mean age was significantly greater in RA patients than in PsA patients (62 years vs. 56 years, respectively). However, after age, sex, and ethnicity were controlled for, the odds of metabolic syndrome remained significantly higher for PsA patients (odds ratio, 1.44).

Metabolic syndrome was defined as a body mass index greater than 30 kg/m² and any two of the following criteria: triglycerides greater than 150 mg/dL, HDL less than 40 mg/dL for men or less than 50 mg/dL for women, a diagnosis of hypertension, or a diagnosis of diabetes.

In a subanalysis of obese patients (133 PsA patients and 654 RA patients with a BMI greater than 30), the prevalence of metabolic syndrome remained significantly higher in PsA patients (60%) than in RA patients (49%), as did the prevalence of patients with triglycerides greater than 150 mg/dL (51% vs. 39%).

The study was limited by the relatively small sample of PsA patients, and by the modified metabolic syndrome criteria that may have underestimated the prevalence of metabolic syndrome in both groups, said Dr. Bahce-Altuntas.

However, the results suggest that metabolic syndrome and its components are significantly more common in PsA than in RA. "High triglycerides appear to drive the estimated increase in risk of metabolic syndrome in PsA vs. RA," she noted.

The combination of skin and joint inflammation in PsA may contribute to the increased frequency of metabolic syndrome in these patients, but more research is needed, Dr. Bahce-Altuntas said.

Meanwhile, "more intensive interventions to modify these risk factors are warranted in PsA patients in order to reduce cardiovascular morbidity and mortality," she said.

The following companies have supported CORRONA through contracted subscriptions over the past 2 years: Abbott, Amgen, AstraZeneca, Bristol-Myers Squibb, Centocor, Genentech, Lilly, Pfizer, and Roche. Dr. Bahce-Altuntas had no financial conflicts to disclose.

CHICAGO – Metabolic syndrome is significantly more common in patients with psoriatic arthritis than in those with rheumatoid arthritis, based on data from nearly 2,000 adults.

Previous studies have suggested that metabolic syndrome is associated with "a state of chronic, low-grade inflammation," said Dr. Asena Bahce-Altuntas of Albert Einstein College of Medicine in New York.

"Since psoriatic arthritis [PsA] is characterized by inflammation of both skin and joints, we may be underestimating this cardiovascular risk in PsA," she said at the annual meeting of the American College of Rheumatology.

To compare the prevalence of metabolic syndrome in patients with PsA versus rheumatoid arthritis (RA), Dr. Bahce-Altuntas and her colleagues used data from the Consortium of Rheumatology Researchers of North America (CORRONA) registry, a prospective, observational cohort including 4,014 patients with PsA and 25,976 patients with RA in academic and private practices throughout the United States. Lipid profile data were available for 1,956 patients from the CORRONA registry: 294 with PsA and 1,662 with RA.

Overall, 27% of PsA patients met criteria for metabolic syndrome, compared with 19% of RA patients. In addition, several specific components of metabolic syndrome were significantly more common in PsA patients.

In particular, significantly more PsA patients than RA patients had triglycerides greater than 150 mg/dL (38% vs. 28%).

Significantly more PsA patients than RA patients were male (54% vs. 23%, respectively), and the mean age was significantly greater in RA patients than in PsA patients (62 years vs. 56 years, respectively). However, after age, sex, and ethnicity were controlled for, the odds of metabolic syndrome remained significantly higher for PsA patients (odds ratio, 1.44).

Metabolic syndrome was defined as a body mass index greater than 30 kg/m² and any two of the following criteria: triglycerides greater than 150 mg/dL, HDL less than 40 mg/dL for men or less than 50 mg/dL for women, a diagnosis of hypertension, or a diagnosis of diabetes.

In a subanalysis of obese patients (133 PsA patients and 654 RA patients with a BMI greater than 30), the prevalence of metabolic syndrome remained significantly higher in PsA patients (60%) than in RA patients (49%), as did the prevalence of patients with triglycerides greater than 150 mg/dL (51% vs. 39%).

The study was limited by the relatively small sample of PsA patients, and by the modified metabolic syndrome criteria that may have underestimated the prevalence of metabolic syndrome in both groups, said Dr. Bahce-Altuntas.

However, the results suggest that metabolic syndrome and its components are significantly more common in PsA than in RA. "High triglycerides appear to drive the estimated increase in risk of metabolic syndrome in PsA vs. RA," she noted.

The combination of skin and joint inflammation in PsA may contribute to the increased frequency of metabolic syndrome in these patients, but more research is needed, Dr. Bahce-Altuntas said.

Meanwhile, "more intensive interventions to modify these risk factors are warranted in PsA patients in order to reduce cardiovascular morbidity and mortality," she said.

The following companies have supported CORRONA through contracted subscriptions over the past 2 years: Abbott, Amgen, AstraZeneca, Bristol-Myers Squibb, Centocor, Genentech, Lilly, Pfizer, and Roche. Dr. Bahce-Altuntas had no financial conflicts to disclose.

NEW YORK – Tocilizumab monotherapy is a viable alternative treatment for patients with moderate to severe rheumatoid arthritis who have not responded to methotrexate in use with the biologic, according to Dr. Yusuf Yazici, speaking at a meeting sponsored by New York University.

"One paradigm of RA treatment is that a biologic alone is equivalent to methotrexate alone, but that the combination is better. These data suggest that tocilizumab may possibly be used alone," said Dr. Yazici, director of the Seligman Center for Advanced Therapeutics and Behçet’s Syndrome Evaluation, Treatment, and Research Center at the NYU Hospital for Joint Diseases.

Data from the ACT-RAY trial, which was presented by Dr. Maxime Dougados, professor of rheumatology at René Descartes University, Cochin Hospital, Paris, at the 2011 annual meeting of the American College of Rheumatology, showed that the DAS28 remission rate was 35% for tocilizumab plus placebo, compared with 40% for tocilizumab plus methotrexate, a difference that was not statistically significant (P = .19; 95% confidence interval, 2.4%-13.7%).

There were also no significant differences among ACR 20/50/70/90 response rates between groups. For both groups, the onset of action was comparable, with 18.1% of the combination group and 15.2% of the tocilizumab monotherapy group achieving remission by week 8.

The ACT-RAY trial is a phase IIIb double-blind 2-year study of biologic-naive adults with moderate to severe active RA who were considered to be inadequate responders to methotrexate. Of the 556 patients enrolled, 279 were randomized to tocilizumab (8 mg/kg every 4 weeks) plus a stable dose of methotrexate and 277 received the same dose of tocilizumab plus placebo for 24 weeks. Radiographs taken of the hands and feet at baseline and 24 weeks were assessed for structural changes.

Secondary outcomes, such as progression of structural damage as measured by the Genant-modified Sharp score (GSS) and joint space narrowing score, also showed no significant differences between treatment groups. On several measures, including total GSS scores, the proportion of patients with no progression of structural damage was similar (for example, 65.3% for the combination treatment vs. 58.7% for tocilizumab monotherapy). Improvements from baseline on the Health-Assessment Questionnaire Disability Index and rheumatoid arthritis quality of life score were comparable.

As far as safety, rates of adverse events, serious adverse events, and serious infections per 100 patient-years were indistinguishable.

"There are other pieces of information pointing in the same direction, where for most of the outcome measures there was no difference between the groups; however, some favored the combination arm. None of the studies by themselves prove that monotherapy is as good as combination treatment, but the data provide information that tocilizumab monotherapy is a good option for some patients," said Dr Yazici.

"It would be good to do a study that looks at truly methotrexate-naive patients with early disease and see how tocilizumab monotherapy compares to methotrexate alone and a combination of tocilizumab with methotrexate.

"While the AMBITION study (Ann. Rheum. Dis. 2010;69:88-96) reported that tocilizumab monotherapy was better than methotrexate alone, one-third of patients had been on methotrexate before the trial but discontinued treatment. Those patients are not going to have as robust a response with methotrexate as those who are truly methotrexate naive."

Dr. Yazici also spoke about the results of the ACT-STAR study, a prospective, 24-week open label trial, which were presented at the 2011 annual meeting of the American College of Rheumatology by Dr. Michael E. Weinblatt, codirector of clinical rheumatology at the Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.

In this trial, the enrolled patients were inadequate responders to anti-tumor necrosis factor (anti-TNF) therapy. No significant differences were found on the ACR 20/50/70 among those treated with tocilizumab monotherapy (8 mg/kg, n = 129) and those who received a combination of tocilizumab plus a DMARD (those in the combination group received either tocilizumab 8 mg/kg throughout the trial (n = 221) while others began with a 4 mg/kg dose which then was raised to 8 mg/kg (n = 322)).

While the study concluded that tocilizumab monotherapy was similar to combination therapy, Dr. Yazici commented that the randomization process used was inadequate as this was an open label trial and the data needs to be interpreted with this in mind. He said, "However, all these studies suggest that there may be a role for tocilizumab monotherapy in patients who have had an inadequate response to methotrexate in the past."

Tocilizumab, a biologic that targets interleukin-6 receptors, was approved in the United States in January 2010 for the treatment of adults with moderate to severe, active RA who have had an inadequate response to one or more TNF inhibitors. Tocilizumab monotherapy could be particularly beneficial for those with RA who respond poorly to methotrexate or experience adverse effects from it.

Dr. Yazici serves as a consultant to Bristol-Myers Squibb and Genentech.

NEW YORK – Tocilizumab monotherapy is a viable alternative treatment for patients with moderate to severe rheumatoid arthritis who have not responded to methotrexate in use with the biologic, according to Dr. Yusuf Yazici, speaking at a meeting sponsored by New York University.

"One paradigm of RA treatment is that a biologic alone is equivalent to methotrexate alone, but that the combination is better. These data suggest that tocilizumab may possibly be used alone," said Dr. Yazici, director of the Seligman Center for Advanced Therapeutics and Behçet’s Syndrome Evaluation, Treatment, and Research Center at the NYU Hospital for Joint Diseases.

Data from the ACT-RAY trial, which was presented by Dr. Maxime Dougados, professor of rheumatology at René Descartes University, Cochin Hospital, Paris, at the 2011 annual meeting of the American College of Rheumatology, showed that the DAS28 remission rate was 35% for tocilizumab plus placebo, compared with 40% for tocilizumab plus methotrexate, a difference that was not statistically significant (P = .19; 95% confidence interval, 2.4%-13.7%).

There were also no significant differences among ACR 20/50/70/90 response rates between groups. For both groups, the onset of action was comparable, with 18.1% of the combination group and 15.2% of the tocilizumab monotherapy group achieving remission by week 8.

The ACT-RAY trial is a phase IIIb double-blind 2-year study of biologic-naive adults with moderate to severe active RA who were considered to be inadequate responders to methotrexate. Of the 556 patients enrolled, 279 were randomized to tocilizumab (8 mg/kg every 4 weeks) plus a stable dose of methotrexate and 277 received the same dose of tocilizumab plus placebo for 24 weeks. Radiographs taken of the hands and feet at baseline and 24 weeks were assessed for structural changes.

Secondary outcomes, such as progression of structural damage as measured by the Genant-modified Sharp score (GSS) and joint space narrowing score, also showed no significant differences between treatment groups. On several measures, including total GSS scores, the proportion of patients with no progression of structural damage was similar (for example, 65.3% for the combination treatment vs. 58.7% for tocilizumab monotherapy). Improvements from baseline on the Health-Assessment Questionnaire Disability Index and rheumatoid arthritis quality of life score were comparable.

As far as safety, rates of adverse events, serious adverse events, and serious infections per 100 patient-years were indistinguishable.

"There are other pieces of information pointing in the same direction, where for most of the outcome measures there was no difference between the groups; however, some favored the combination arm. None of the studies by themselves prove that monotherapy is as good as combination treatment, but the data provide information that tocilizumab monotherapy is a good option for some patients," said Dr Yazici.

"It would be good to do a study that looks at truly methotrexate-naive patients with early disease and see how tocilizumab monotherapy compares to methotrexate alone and a combination of tocilizumab with methotrexate.

"While the AMBITION study (Ann. Rheum. Dis. 2010;69:88-96) reported that tocilizumab monotherapy was better than methotrexate alone, one-third of patients had been on methotrexate before the trial but discontinued treatment. Those patients are not going to have as robust a response with methotrexate as those who are truly methotrexate naive."

Dr. Yazici also spoke about the results of the ACT-STAR study, a prospective, 24-week open label trial, which were presented at the 2011 annual meeting of the American College of Rheumatology by Dr. Michael E. Weinblatt, codirector of clinical rheumatology at the Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.

In this trial, the enrolled patients were inadequate responders to anti-tumor necrosis factor (anti-TNF) therapy. No significant differences were found on the ACR 20/50/70 among those treated with tocilizumab monotherapy (8 mg/kg, n = 129) and those who received a combination of tocilizumab plus a DMARD (those in the combination group received either tocilizumab 8 mg/kg throughout the trial (n = 221) while others began with a 4 mg/kg dose which then was raised to 8 mg/kg (n = 322)).

While the study concluded that tocilizumab monotherapy was similar to combination therapy, Dr. Yazici commented that the randomization process used was inadequate as this was an open label trial and the data needs to be interpreted with this in mind. He said, "However, all these studies suggest that there may be a role for tocilizumab monotherapy in patients who have had an inadequate response to methotrexate in the past."

Tocilizumab, a biologic that targets interleukin-6 receptors, was approved in the United States in January 2010 for the treatment of adults with moderate to severe, active RA who have had an inadequate response to one or more TNF inhibitors. Tocilizumab monotherapy could be particularly beneficial for those with RA who respond poorly to methotrexate or experience adverse effects from it.

Dr. Yazici serves as a consultant to Bristol-Myers Squibb and Genentech.

NEW YORK – Tocilizumab monotherapy is a viable alternative treatment for patients with moderate to severe rheumatoid arthritis who have not responded to methotrexate in use with the biologic, according to Dr. Yusuf Yazici, speaking at a meeting sponsored by New York University.

"One paradigm of RA treatment is that a biologic alone is equivalent to methotrexate alone, but that the combination is better. These data suggest that tocilizumab may possibly be used alone," said Dr. Yazici, director of the Seligman Center for Advanced Therapeutics and Behçet’s Syndrome Evaluation, Treatment, and Research Center at the NYU Hospital for Joint Diseases.

Data from the ACT-RAY trial, which was presented by Dr. Maxime Dougados, professor of rheumatology at René Descartes University, Cochin Hospital, Paris, at the 2011 annual meeting of the American College of Rheumatology, showed that the DAS28 remission rate was 35% for tocilizumab plus placebo, compared with 40% for tocilizumab plus methotrexate, a difference that was not statistically significant (P = .19; 95% confidence interval, 2.4%-13.7%).

There were also no significant differences among ACR 20/50/70/90 response rates between groups. For both groups, the onset of action was comparable, with 18.1% of the combination group and 15.2% of the tocilizumab monotherapy group achieving remission by week 8.

The ACT-RAY trial is a phase IIIb double-blind 2-year study of biologic-naive adults with moderate to severe active RA who were considered to be inadequate responders to methotrexate. Of the 556 patients enrolled, 279 were randomized to tocilizumab (8 mg/kg every 4 weeks) plus a stable dose of methotrexate and 277 received the same dose of tocilizumab plus placebo for 24 weeks. Radiographs taken of the hands and feet at baseline and 24 weeks were assessed for structural changes.

Secondary outcomes, such as progression of structural damage as measured by the Genant-modified Sharp score (GSS) and joint space narrowing score, also showed no significant differences between treatment groups. On several measures, including total GSS scores, the proportion of patients with no progression of structural damage was similar (for example, 65.3% for the combination treatment vs. 58.7% for tocilizumab monotherapy). Improvements from baseline on the Health-Assessment Questionnaire Disability Index and rheumatoid arthritis quality of life score were comparable.

As far as safety, rates of adverse events, serious adverse events, and serious infections per 100 patient-years were indistinguishable.

"There are other pieces of information pointing in the same direction, where for most of the outcome measures there was no difference between the groups; however, some favored the combination arm. None of the studies by themselves prove that monotherapy is as good as combination treatment, but the data provide information that tocilizumab monotherapy is a good option for some patients," said Dr Yazici.

"It would be good to do a study that looks at truly methotrexate-naive patients with early disease and see how tocilizumab monotherapy compares to methotrexate alone and a combination of tocilizumab with methotrexate.

"While the AMBITION study (Ann. Rheum. Dis. 2010;69:88-96) reported that tocilizumab monotherapy was better than methotrexate alone, one-third of patients had been on methotrexate before the trial but discontinued treatment. Those patients are not going to have as robust a response with methotrexate as those who are truly methotrexate naive."

Dr. Yazici also spoke about the results of the ACT-STAR study, a prospective, 24-week open label trial, which were presented at the 2011 annual meeting of the American College of Rheumatology by Dr. Michael E. Weinblatt, codirector of clinical rheumatology at the Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.

In this trial, the enrolled patients were inadequate responders to anti-tumor necrosis factor (anti-TNF) therapy. No significant differences were found on the ACR 20/50/70 among those treated with tocilizumab monotherapy (8 mg/kg, n = 129) and those who received a combination of tocilizumab plus a DMARD (those in the combination group received either tocilizumab 8 mg/kg throughout the trial (n = 221) while others began with a 4 mg/kg dose which then was raised to 8 mg/kg (n = 322)).

While the study concluded that tocilizumab monotherapy was similar to combination therapy, Dr. Yazici commented that the randomization process used was inadequate as this was an open label trial and the data needs to be interpreted with this in mind. He said, "However, all these studies suggest that there may be a role for tocilizumab monotherapy in patients who have had an inadequate response to methotrexate in the past."

Tocilizumab, a biologic that targets interleukin-6 receptors, was approved in the United States in January 2010 for the treatment of adults with moderate to severe, active RA who have had an inadequate response to one or more TNF inhibitors. Tocilizumab monotherapy could be particularly beneficial for those with RA who respond poorly to methotrexate or experience adverse effects from it.

Dr. Yazici serves as a consultant to Bristol-Myers Squibb and Genentech.